GCK, GCKR polymorphisms and risk of chronic kidney disease in Japanese individuals: Data from the J-MICC Study

Background: 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. Methods: The subjects for this analysis were 3,314 consecutively selected participants from the Japan Multi- Institutional Collaborative Cohort Study. Age- and sexadjusted 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. Results: 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. Conclusion: 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.