GCK, GCKR polymorphisms and risk of chronic kidney disease in Japanese individuals: data from the J-MICC Study
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Chronic kidney disease (CKD) is well known as a strong risk factor for both of end-stage renal disease and cardiovascular disease. To clarify the association of glucokinase and glucokinase regulatory protein (GCKR) polymorphisms with the risk of CKD in Japan, we examined this association among Japanese individuals using cross-sectional data.
The subjects for this analysis were 3,314 consecutively selected participants from the Japan Multi-Institutional Collaborative Cohort Study. Age- and sex- adjusted odds ratios (aORs) of CKD stages 3–5 were calculated for each genotype by logistic regression and the effects of genotype on estimated glomerular filtration rate were evaluated by linear regression. Gene–environment interaction was also investigated based on questionnaire information.
When subjects with GCKR rs780094 G/A and G/G, or GCKR rs1260326 T/C and C/C were combined together and compared with the references (GCKR rs780094 A/A or GCKR rs1260326 T/T), the aORs were 0.84 (0.69–1.02) or 0.81 (0.67–0.99) (p = 0.075 or 0.037), respectively. A significant OR for interaction between GCKR rs1260326 T/T and current smoking (OR = 1.79, p = 0.041) was also observed.
The present study suggests a possible association of the T/T genotype of GCKR rs1260326 polymorphism with elevated risk of CKD and its interaction with current smoking, which may support the possibility of performing risk evaluation and prevention of this potentially life-threatening disease based on genetic traits in the near future.
KeywordsChronic kidney disease GCK & GCKR polymorphisms Lifestyle factors Renal insufficiency
The authors wish to thank Mr. Kyota Ashikawa and Ms. Tomomi Aoi at the Laboratory of Genotyping Development, Center for Genomic Medicine, RIKEN for genotyping. The authors also thank Ms. Yoko Mitsuda, and Ms Keiko Shibata at Daiko Medical Center, Nagoya University for their technical assistance.
This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas of Cancer (No. 17015018) and Scientific Support Programs for Cancer Research, Grant-in-Aid for Scientific Research on Innovative Areas (No. 221S0001) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
Conflict of interest
The authors have no conflicts of interest to disclose.
Experimental investigation on human subjects
The study was in adherence with the Declaration of Helsinki. All the data were obtained after acquiring the informed consent from all the participants; and the study protocol was approved by the institutional review board of Nagoya University Graduate School of Medicine.
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