Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Shino Suma Last modified date:2021.06.28

Assistant Professor / Division of oral health, growth and development / Department of Dental Science / Faculty of Dental Science

1. Suma S, Furuta M, Takeuchi K, Tomioka M, Iwasa Y, Yamashita Y, Number of teeth, denture wearing and cognitive function in relation to nutritional status in residents of nursing homes., Gerodontology, 10.1111/ger.12554, 2021.05.
2. Kuroe K, Furuta M, Takeuchi K, Takeshita T, Suma S, Shinagawa T, Shimazaki Y, Yamashita Y, Association between periodontitis and fibrotic progression of non-alcoholic fatty liver among Japanese adults., J Clin Periodontol, 10.1111/jcpe.13415, 48, 3, 368-377, 2021.03.
3. Furuta M, Takeuchi K, Takeshita T, Tanaka A, Suma S, Shinagawa T, Shimazaki Y, Yamashita Y, Longitudinal Associations of Toothbrushing With Obesity and Hyperglycemia., J Epidemiol, 10.2188/jea.JE20190165, 30, 12, 556-565, 2020.06.
4. Suma S, Furuta M, Yamashita Y, Matsushita K, Aging, Mastication, and Malnutrition and Their Associations with Cognitive Disorder: Evidence from Epidemiological Data, Curr Oral Health Rep, 10.1007/s40496-019-0220-8, 6, 2, 89-99, 2019.06.
5. Takeuchi K, Matsumoto K, Furuta M, Fukuyama S, Takeshita T, Ogata H, Suma S, Shibata Y, Shimazaki Y, Hata J, Ninomiya T, Nakanishi Y, Inoue H, Yamashita Y, Periodontitis Is Associated with Chronic Obstructive Pulmonary Disease., J Dent Res, 10.1177/0022034519833630, 98, 5, 534-540, 2019.05.
6. Yatabe N, Takeuchi K, Izumi M, Furuta M, Takeshita T, Shibata Y, Suma S, Kageyama S, Ganaha S, Tohara H, Yamashita Y, Decreased cognitive function is associated with dysphagia risk in nursing home older residents., Gerodontology, 10.1111/ger.12366, 35, 4, 376-381, 2018.12.
7. Takeuchi K, Matsumoto K, Furuta M, Fukuyama S, Takeshita T, Ogata H, Suma S, Shibata Y, Shimazaki Y, Hata J, Ninomiya T, Nakanishi Y, Inoue H, Yamashita Y, Periodontal status and lung function decline in the community: the Hisayama study., Sci Rep, 10.1038/s41598-018-31610-3, 8, 1, 13354, 2018.09.
8. Shino Suma, Yutak Watanabe, Hirohiko Hirano, Ai Kimura, Ayako Edahiro, Shuichi Awata, Yoshihisa Yamashita, Kenji Matsushita, Hidenori Arai, Takashi Sakurai, Factors affecting the appetites of persons with Alzheimer's disease and mild cognitive impairment., Geriatr Gerontol Int, 10.1111/ggi.13455, 2018.05, AIM:
Appetite loss has been associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Among older people, decreased appetite can result in poor nutrition and subsequent loss of independent living. We examined the factors related to appetite loss in persons with AD and MCI to provide evidence for countermeasures to prevent appetite loss and progression of cognitive impairment.

We included 1238 older adults undergoing outpatient treatment at the Center for Comprehensive Care and Research on Memory Disorders (Medical Center for Dementia) at the National Center for Geriatrics and Gerontology in Obu, Japan. The Council on Nutrition Appetite Questionnaire, an appetite questionnaire for older people, was used to evaluate appetite. Appetite loss in persons diagnosed with AD or MCI was divided into two groups according to the Council on Nutrition Appetite Questionnaire scores, and logistic regression analysis was carried out to identify independent factors associated with appetite loss. The following variables were used to evaluate for covariates: general information, functional evaluation and medications.

The AD and MCI groups contained 853 and 385 individuals, respectively. In both groups, depression and difficulty in maintaining attention while eating were significantly associated with poor appetite. Among persons with AD, lower vitality, more comorbidities, non-use of antidementia drugs and use of psychotropic drugs were also significantly associated with poor appetite.

The present study recognized possible factors individually associated with appetite loss among persons with AD or MCI. Future studies are required to examine supportive strategies to treat poor appetite in these populations..
9. Shino Suma, Mariko Naito, Kenji Wakai, Toru Naito, Masaaki Kojima, Osami Umemura, Makoto Yokota, Nobuyuki Hanada, Takashi Kawamura, Tooth loss and pneumonia mortality: A cohort study of Japanese dentists., PLoS One, 10.1371/journal.pone.0195813, 13, 4, 2018.04, Although associations between oral health and pneumonia have been reported in previous studies, particularly in the institutionalized elderly, few prospective studies have investigated the association between oral condition and pneumonia among community-dwelling people and whether the findings among inpatients or patients in nursing homes are applicable to the general population is still unclear. The oral bacteria propagated in the periodontal regions may drop into the lung and increase the risk of pneumonia. We, therefore, investigated the association of tooth loss with mortality from pneumonia in a cohort study of Japanese dentists. Members of the Japan Dental Association (JDA) participated in the LEMONADE (Longitudinal Evaluation of Multi-phasic, Odontological and Nutritional Associations in Dentists) Study. From 2001 to 2006, they completed a baseline questionnaire on lifestyle and health factors including the number of teeth lost (excluding third molars). We followed 19,775 participants (mean age ± standard deviation, 51.4 ± 11.7 years; 1,573 women [8.0%] and 18,202 men [92.0%]) for mortality from pneumonia (ICD-10, J12-J18). Mortality data were collected via the fraternal insurance program of the JDA. The hazard ratios (HRs) were estimated with adjustment for sex, age, body mass index, smoking status, physical activity and diabetes history. During the median follow-up period of 9.5 years, we documented 68 deaths from pneumonia. Participants who were edentulous at baseline were at significantly increased risk of mortality from pneumonia. The multivariable-adjusted HRs were 2.07 (95% confidence interval [CI], 1.09-3.95) for the edentulous and 1.60 (95% CI, 0.83-3.10) for loss of 15-27 teeth relative to loss of 0-14 teeth (trend p = 0.026). The HR per one tooth loss was also significant; 1.031 (95% CI, 1.004-1.060). In conclusion, a large number of teeth lost may indicate an increased risk of mortality from pneumonia in community-dwelling populations..
10. Kenji Takeuchi, Michiko Furuta, Yuka Okabe, Shino Suma, Toru Takeshita, Sumio Akifusa, Munehisa Adachi, Toshinori Kinoshita, Takeshi Kikutani, Yoshihisa Yamashita, Swallowing disorders and 1-year functional decline in community-dwelling older adults receiving home care., J Oral Rehabil, 10.1111/joor.12577, 44, 12, 982-987, 2017.12, The purpose of this study was to clarify the effect of swallowing disorders on functional decline in community-dwelling older adults receiving home care. This was a 1-year follow-up survey of 176 individuals ≥60 years living at home and receiving homecare services, without total dependence in basic daily living activities, in two mid-sized municipalities in Fukuoka, Japan. Functional decline was measured using the Barthel index (BI), and the primary outcome was total dependence in basic daily living activities (BI ≤ 20 points). Swallowing function was assessed using cervical auscultation, and the primary predictor was swallowing disorders. Logistic regression models were used to assess univariate and multivariate associations between baseline swallowing function and functional decline during follow-up. During follow-up 16 (9.1%), the participants became totally dependent in basic daily living activities. The participants with swallowing disorders had 6.41 times higher odds of total dependence in basic daily living activities compared to participants with normal swallowing function. After adjusting for potential confounders, swallowing disorders were significantly associated with higher odds of total dependence in basic daily living activities (odds ratio = 5.21, 95% confidence interval = 1.33-20.44). Regarding swallowing disorders, the corresponding population attributable fraction (%) of the incidence of total dependence in basic daily living activities was 50.4%. The current findings demonstrated that swallowing disorders were associated with greater risk of functional decline in basic daily living activities among older adults living at home and receiving home nursing care. Maintenance and improvement of swallowing function may prevent late-life functional decline..
11. Shinya Kageyama, Toru Takeshita, Michiko Furuta, Mikiko Tomioka, Mikari Asakawa, Shino Suma, Kenji Takeuchi, Yukie Shibata, Yasuyuki Iwasa, Yoshihisa Yamashita, Relationships of variations in the tongue microbiota and pneumonia mortality in nursing home residents., J Gerontol A Biol Sci Med Sci, 10.1093/gerona/glx205, 2017.10, BACKGROUND:
Aspiration of oral debris, containing dense oral bacteria, is a major cause of pneumonia in elderly adults. This study investigated the relationship between tongue microbiota composition and incidence of pneumonia-related deaths, in nursing home residents.

The subjects were assessed for health conditions, including their tongue microbiota, at baseline. We determined tongue microbiota profiles by 16S ribosomal RNA gene sequencing and clustering approach. All subjects (n = 173) were followed prospectively for a median of 19 months to assess the incidence of all-cause death, including pneumonia-related death. We evaluated risk estimates of microbiota effects on death using multivariate Cox proportional hazards regression analysis.

Tongue microbiota were classified into two community types: type I was dominated by Prevotella and Veillonella species, while type II was dominated by Neisseria and Fusobacterium species. The subjects with type I microbiota exhibited a significantly greater risk of all-cause death (adjusted hazard ratio [aHR] = 3.79, 95% confidence interval [CI] = 1.38-10.39) and pneumonia-related death (aHR = 13.88, 95% CI = 1.64-117.21), than those with type II microbiota. There was no significant association between microbiota type and other-cause death.

The tongue microbiota type was significantly associated with an increased mortality risk from pneumonia in nursing home residents..
12. Yuta Hattori, Mariko Naito, Masahiko Satoh, Masahiro Nakatochi, Hisao Naito, Masashi Kato, Sahoko Takagi, Takashi Matsunaga, Toshio Seiki, Tae Sasakabe, Shino Suma, Sayo Kawai, Rieko Okada, Asahi Hishida, Nobuyuki Hamajima, Kenji Wakai, Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies., TOXICOL SCI, 10.1093/toxsci/kfw080, 152, 1, 181-193, 2016.07, Metallothioneins (MTs) are proteins that protect cells from toxic agents such as heavy metal ions or reactive oxygen species. MT2A A-5G is a single nucleotide polymorphism in the promoter region of the MT2A gene, and the minor G allele results in lower transcription efficiency. We aimed to elucidate associations between MT2A A-5G and risks of 2 diseases potentially related to lowered MT expression, chronic kidney disease (CKD), and diabetes mellitus (DM), in a community-dwelling population. Study subjects were Nagoya city residents participating in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC) Daiko Study, comprised 749 men and 2,025 women, aged 39-75 years. CKD (>stage 3) and DM were defined by standard guidelines. Associations were evaluated using logistic regression models with adjustments for age, sex and potential confounders in a cross-sectional study, and verified in a 5-year longitudinal study. Odds ratios (OR [95% confidence interval]) were calculated relative to the AA genotype. Serum MT (I + II), Cd and zinc levels were also determined by genotype. The OR of the GG genotype for CKD risk was 3.98 (1.50, 10.58) in the cross-sectional study and 5.17 (1.39, 19.28) in the longitudinal study. The OR of the GA genotype for DM was 1.86 (1.26, 2.75) in the cross-sectional study and 2.03 (1.19, 3.46) in the longitudinal study. MT2A A-5G may be associated with CKD and DM risks. This polymorphism is a promising target for evaluations of CKD and DM risks with possible involvement of low-dose chronic exposure to environmental pollutants..
13. Masayuki Sakiyama, Hirotaka Matsuo, Seiko Shimizu, Hiroshi Nakashima, Takahiro Nakamura, Akiyoshi Nakayama, Toshihide Higashino, Mariko Naito, Shino Suma, Asahi Hishida, Takahiro Satoh, Yutaka Sakurai, Tappei Takada, Kimiyoshi Ichida, Hiroshi Ooyama, Toru Shimizu, Nariyoshi Shinomiya, The effects of URAT1/SLC22A12 nonfunctional variants, R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression, SCIENTIFIC REPORTS, 10.1038/srep20148, 6, 2016.01, Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 × 10(-46)). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 × 10(-19); risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia, and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction = 1.5 × 10(-12)). .
14. Miwa Yamaguchi, Hirokazu Uemura, Kokichi Arisawa, Sakurako Katsuura-Kamano, Nobuyuki Hamajima, Asahi Hishida, Shino Suma, Isao Oze, Kazuyo Nakamura, Naoyuki Takashima, Sadao Suzuki, Rie Ibusuki, Haruo Mikami, Keizo Ohnaka, Nagato Kuriyama, Michiaki Kubo, Hideo Tanaka, Association between brain-muscle-ARNT-like protein-2 (BMAL2) gene polymorphism and type 2 diabetes mellitus in obese Japanese individuals: A cross-sectional analysis of the Japan Multi-institutional Collaborative Cohort Study, INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 10.1016/j.diabres.2015.10.009, 110, 3, 301-308, 2015.12, AIMS: Brain-muscle-Arnt-like protein-1 (BMAL1) and BMAL2 genes are essential components of the circadian clock, and are considered to be involved in glucose homeostasis. We examined whether single nucleotide polymorphisms (SNPs) of BMAL1 and BMAL2 were associated with the prevalence of type 2 diabetes (T2DM) in the general Japanese population.
METHODS: We studied 2467 subjects (1232 men and 1235 women, 35-69 years old), including 105 men and 57 women with T2DM, from the participants of the Japan Multi-institutional Collaborative Cohort Study. The association between SNPs in the BMAL1 (rs11022775 and rs2290035) and BMAL2 (rs7958822) genes and T2DM were analyzed by multiple logistic regression after adjustment for potential confounders. Analysis was also performed after stratification by body mass index (≥25 kg/m(2) and <25 kg/m(2)) to investigate an interaction between genotypes and obesity.
RESULTS: The A/G and A/A genotypes of BMAL2 rs7958822 showed significantly higher adjusted odds ratios (OR) for T2DM than the G/G genotype among obese men (OR=2.2, 95% confidence intervals [CI] 1.1, 4.6, P for interaction=0.0495) and obese women (OR=2.7, 95% CI 1.1, 6.7, P for interaction=0.199). There were no significant associations between BMAL1 rs11022775 or rs2290035 genotypes and T2DM.
CONCLUSIONS: To the best of our knowledge, this is the first study to show the significant association between BMAL2 rs7958822 genotype and T2DM among obese subjects..
15. Takashi Tamura, Emi Morita, Sayo Kawai, TaeSasakabe, Yuka Sugimoto, Nana Fukuda, Shino Suma, Hiroko Nakagawa, Rieko Okada, Asahi Hishida, Mariko Naito, Nobuyuki Hamajima, Kenji Wakai, No association between Helicobacter pylori infection and diabetes mellitus among a general Japanese population: a cross-sectional study, SPRINGERPLUS, 10.1186/s40064-015-1371-2, 4, 2015.10, Several case-control studies have reported that patients with diabetes mellitus (DM) had a higher prevalence of Helicobacter pylori infection than those without DM, but these findings remain equivocal. Additionally, there are few studies examining associations between East Asian CagA-positive H. pylori and DM. This cross-sectional study aimed to investigate whether H. pylori infection was a possible risk factor for DM in a general Japanese population. The study included 5165 subjects (1467 men, 3698 women) aged 35-69 years from the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. A urinary anti-H. pylori antibody was used to detect H. pylori infection. The medical history of physician-diagnosed DM was confirmed by self-administered questionnaire. The odds ratios (ORs) and their 95 % confidence intervals (CIs) for DM (current and former) were calculated using unconditional logistic regression analysis, adjusting for age, sex, educational status, alcohol use, smoking status, body mass index, energy intake, and physical activity. The prevalence of DM was 4.6 % (95 % CI 3.7-5.6 %) among 1878 participants with H. pylori infection and 3.2 % (2.6-3.8 %) among 3287 without the infection (p = 0.009). The crude, age-adjusted, and multivariate-adjusted ORs for DM in those with the infection relative to those without were 1.47 (95 % CI 1.10-1.97), 1.02 (0.76-1.38), and 0.97 (0.71-1.32), respectively. We found a significantly higher DM prevalence among those with H. pylori infection than among those without. However, almost all the difference in prevalence could be explained by the older age of those infected. Our findings did not support an association between H. pylori infection and DM. .
16. Shino Suma, Mariko Naito, Kenji Wakai, Tae Sasakabe, Yuta Hattori, Rieko Okada, Sayo Kawai, Asahi Hishida, Emi Morita, Hiroko Nakagawa, Takashi Tamura, Nobuyuki Hamajima, Effects of IL6 C-634G polymorphism on tooth loss and their interaction with smoking habits, ORAL DISEASES, 10.1111/odi.12352, 21, 6, 807-813, 2015.09, OBJECTIVE: To examine the association between an IL6 (Interleukin-6) polymorphism (C-634G or rs1800796) and tooth loss, and an interaction between the polymorphism and smoking habits for the loss.
MATERIAL AND METHODS: Our subjects were 4917 check-up examinees ages 35-69. They reported tooth loss and lifestyle in a questionnaire. We regressed the number of teeth on the IL6 genotype, gender, age, smoking, drinking, diabetes, hypertension, physical activity, energy intake, education, and brushing. We further estimated multivariate-adjusted odds ratios (ORs) for having <20 teeth.
RESULTS: Participants with a GG genotype tended to have less teeth than those with CC; β = -0.798 (95% confidence interval [CI] = -1.501--0.096). Subjects with a GG genotype were more likely to have <20 teeth than those with CC; OR was 1.56 (95% CI = 1.08-2.25). Association between current smoking and tooth loss was stronger among those with GG than among those with CC. In a multiple regression analysis, a significant interaction was found between GG genotype and current smoking in the prediction of tooth loss (P = 0.018).
CONCLUSION: The IL6 C-634G polymorphism was significantly associated with tooth loss. Our results suggest greater effects of smoking on tooth loss in GG genotype individuals.
17. Junichiro Mokuno, Asahi Hishida, Emi Morita, Tae Sasakabe, Shino Suma, Yuta Hattori, Rieko Okada, Sayo Kawai, Mariko Naito, Kenji Wakai, ATP-binding cassette transporter A1 (ABCA1) R219K (G1051A, rs2230806) polymorphism and serum high-density lipoprotein cholesterol levels in a large Japanese population: cross-sectional data from the Daiko Study, ENDOCRINE JOURNAL, 62, 6, 543-549, 2015.06.
18. Yuka Sugimoto, Kenji Wakai, Hiroko Nakagawa, Shino Suma, Tae Sasakabe, Tatsuhiko Sakamoto, Naoyuki Takashima, Sadao Suzuki, Shin Ogawa, Keizo Ohnaka, Nagato Kuriyama, Kokichi Arisawa, Haruo Mikami, Michiaki Kubo, Satoyo Hosono, Nobuyuki Hamajima, Hideo Tanaka, Associations between polymorphisms of interleukin-6 and related cytokine genes and serum liver damage markers: a cross-sectional study in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, GENE, 10.1016/j.gene.2014.12.025, 557, 2, 158-162, 2015.02, Cytokines, including interleukin-6 (IL-6), play an important role in the liver. The aim of this study was to investigate associations between common polymorphisms in potential functional promoters of cytokine genes and liver damage markers among enrollees of a large Japanese cohort study. Subjects included 3257 Japanese individuals (1608 men and 1649 women, aged 35-69 years). Six single nucleotide polymorphisms (SNPs) in the promoter regions of five cytokine genes, IL1B (T-31C), IL6 (C-634G), IL8 (T-251A), IL10 (T-819C), tumor necrosis factor-A (TNFA) (T-1031C), and TNFA (C-857T), were genotyped by polymerase chain reaction. Information regarding alcohol intake, smoking habits, height, and weight was collected by a self-administered questionnaire. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured during a routine health check-up. Of the six SNPs genotyped, an IL6 polymorphism (rs1800796, C-634G) was most strongly associated with a liver damage marker, AST. Mean serum AST was significantly different among the three genotypes (mean ± SD, 22.7 ± 7.3 IU/L for CC, 22.8 ± 7.7 IU/L for CG, and 24.3 ± 8.6 IU/L for GG, p=0.011 by analysis of variance). The differences remained significant after adjustment for potential confounders by general linear models. The variations in mean serum AST and ALT levels were marked especially among men. Thus, the functional polymorphism IL6 C-634G may affect serum AST and ALT levels, possibly through different IL-6 production..
19. Toshinori Chiba, Hirotaka Matsuo, Akiyoshi Nakayama, Seiko Shimizu, Kenji Wakai, Shino Suma, Hiroshi Nakashima, Yutaka Sakurai, Toru Shimizu, Kimiyoshi Ichida, Nariyoshi Shinomiya, Common variant of ALPK1 is not associated with gout: a replication study, HUMAN CELL, 10.1007/s13577-014-0103-1, 28, 1, 1-4, 2015.01, Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21-31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. However, no replication study has been performed to confirm this association. Therefore, we first conducted a replication study with clinically defined gout patients in a different population. Linkage disequilibrium (LD) analyzes of the 3 SNPs in ALPK1 revealed that these SNPs are in strong LD in a Japanese population. Among the 3 SNPs of ALPK1, rs11726117 (M861T) is the only missense SNP. Therefore, rs11726117 was genotyped in a Japanese population of 903 clinically defined gout cases and 1,302 controls, and was evaluated for a possible association with gout. The minor allele frequencies of rs11726117 were 0.26 and 0.25 in the case and control groups, respectively. The association analysis has not detected a significant association between rs11726117 and gout susceptibility in a Japanese population (p = 0.44). Because ABCG2, a major causative gene for gout, also locates in the gout-susceptibility locus on chromosome 4q, these findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene. .
20. Asahi Hishida, Kenji Wakai, Mariko Naito, Shino Suma, Tae Sasakabe, Nobuyuki Hamajima, Satoyo Hosono, Mikako Horita, Tanvir Chowdhury Turin, Sadao Suzuki, Tara Sefanya Kairupan, Haruo Mikami, Keizo Ohnaka, Isao Watanabe, Hirokazu Uemura, Michiaki Kubo, Hideo Tanaka, Polymorphisms of genes involved in lipid metabolism and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study, LIPIDS IN HEALTH AND DISEASE, 10.1186/1476-511X-13-162, 13, 2014.10, BACKGROUND: Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
METHODS: A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2).
RESULTS: Logistic regression analysis revealed that SNPs APOA5 T - 1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06-1.39), 1.19 (1.03-1.37), 1.27 (1.12-1.45), and 0.81 (0.71-0.92), respectively. Analysis of the gene-environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T - 1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ≥30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29-84.19) and 3.36 (0.87-13.01), respectively.
CONCLUSIONS: Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease.
21. Toshinori Chiba, Hirotaka Matsuo, Yusuke Kawamura, Shushi Nagamori, Takashi Nishiyama, Ling Wei, Akiyoshi Nakayama, Takahiro Nakamura, Masayuki Sakiyama, Tappei Takada, Yutaka Taketani, Shino Suma, Mariko Naito, Takashi Oda, Hiroo Kumagai, Yoshinori Moriyama, Kimiyoshi Ichida, Toru Shimizu, Yoshikatsu Kanai, NPT1/SLC17A1 Is a Renal Urate Exporter in Humans and Its Common Gain-of-Function Variant Decreases the Risk of Renal Underexcretion Gout, ARTHRITIS & RHEUMATOLOGY, 10.1002/art.38884, 67, 1, 281-287, 2015.01, OBJECTIVE: Serum uric acid (SUA) levels in humans are mainly regulated by urate transporters. Recent genome-wide association studies suggested that common variants of the human sodium-dependent phosphate cotransporter type 1 gene (NPT1/SLC17A1) influence SUA. NPT1 has been reported to mediate urate transport, but its physiologic role in regulating SUA in humans remains unclear. Furthermore, the findings of replication studies of the relationship between NPT1 variants and gout have been inconsistent. The aims of this study were to investigate the effect of NPT1 on gout and to determine its physiologic role.
METHODS: Five hundred forty-five male Japanese patients with gout and 1,115 male Japanese control subjects were genotyped for rs1165196 (I269T), a common missense variant in NPT1. Analyses of the association between rs1165196 and gout were then conducted, focusing especially on renal underexcretion (RUE) gout. Immunohistochemical analysis and functional analysis using Xenopus oocytes were also performed.
RESULTS: Single-nucleotide polymorphism rs1165196 significantly decreased the risk of RUE gout (odds ratio 0.73, P = 0.031) but did not confer a risk for all gout (P = 0.123). The immunohistochemical analysis revealed that human NPT1 is localized to the apical membrane of the renal proximal tubule. The functional analysis using Xenopus oocyte expression systems showed that rs1165196 increases NPT1-mediated urate export.
CONCLUSION: This study showed that NPT1 is a urate exporter located in the renal proximal tubule in humans, and that its common gain-of-function variant, rs1165196, causes RUE gout, a major subtype of gout. These findings enable us to deepen our understanding of the physiologic role of NPT1 as a renal urate exporter as well as its pathophysiologic role in gout..
22. Shino Suma, Mariko Naito, Rieko Okada, Sayo Kawai, Guang Yin, Emi Morita, Kenji Wakai, Hirotaka Matsuo, Nobuyuki Hamajima, ASSOCIATIONS BETWEEN BODY MASS INDEX AND SERUM URIC ACID LEVELS IN A JAPANESE POPULATION WERE SIGNIFICANTLY MODIFIED BY LRP2 rs2544390, NAGOYA JOURNAL OF MEDICAL SCIENCE, 76, 3-4, 333-339, 2014.08, The genome-wide association study identified associations between the LRP2 polymorphism rs2544390 and serum uric acid (SUA) levels in a Japanese population. Our previous study on the LRP2 rs2544390 polymorphism identified an interaction between SUA and alcohol consumption. Here, we investigated an interaction with body mass index (BMI) using the same dataset. Subjects were 3,742 health checkup examinees (2,544 males and 1,198 females) aged 35-69 years. Those with the SLC22A12 258WW genotype, SLC2A9 rs11722228 C allele, and ABCG2 126QQ genotype and 141Q allele were selected for analysis to remove the strong influences of these genetic traits. In males, the odds ratio of BMI ≥25.0 relative to BMI <18.5 for hyperuricemia (SUA ≥7 mg/dL and/or under medication for hyperuricemia) was 6.58 (95% confidence interval [CI], 0.84-51.32) for CC, 10.08 (2.38-42.83) for CT, and 2.53 (0.54-11.78) for TT. The interaction was 0.59 (p=0.029) from the model including BMI (<25.0 and ≥25.0), genotype (CC/CT and TT), and the multiplicative interaction term between BMI ≥25.0 and the TT genotype. In females, the odds ratio of BMI ≥25.0 relative to BMI <18.5 for high SUA (≥5 mg/dL and/or under medication for hyperuricemia) was 6.35 (95%CI, 1.68-24.08) for CC, 4.55 (1.85-11.18) for CT, and 5.93 (1.97-17.90) for TT. The interaction term was significant in the opposite direction for females (OR=2.75, p=0.011). The association between BMI and SUA was therefore modified by the LRP2 polymorphism in this Japanese population. .