Gene‐environment interaction in chronic kidney disease among people with type 2 diabetes from The Malaysian Cohort project: a case‐control study

Aim To examine the possible gene‐environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease. Methods A case‐control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene‐environment interaction analyses. Results Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene‐environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person‐years (95% CI: 115, 153), with a mean follow‐up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene‐environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI). Conclusions Our findings suggest that the gene‐environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease. What’s new? In parallel with genotyping advancement, the number of gene‐environment interaction studies has grown substantially. This study tries to elucidate the possible gene‐environment interactions between single nucleotide polymorphisms and environmental factors that could modify the probability for chronic kidney disease among people with type 2 diabetes where local data is scarce. This study suggests that four single nucleotide polymorphisms interact significantly with specifi