Association Study On The Interaction Of CD36 Gene Polymorphisms And Environmental Factors With The Risk Of Type 2 Diabetes Mellitus

ObjectivesTo investigate the association of cluster of differentiation 36 gene?CD36?polymorphisms with type 2 diabetes mellitus?T2DM?susceptibility and related cardio-metabolic indicators,and to evaluate the pair-wise and multi-factor interaction between CD36 variants and environmental risk factors on T2DM risk.MethodsSubjects of this nested case-control study were selected from the Rural Chinese Cohort Study.We randomly selected 546 cases of T2DM as index cases from the newly identified incident cases during the follow-up period.Each case was matched individually with a non-T2DM control randomly with age?within 2 years?,gender,marital status,and residence village as matching conditions.We selected four SNPs within the CD36 gene in this study,including rs1194197,rs2151916,rs3211956,and rs7755.Genotyping was performed by 48-Plex SNPscan^TM Genotyping system.Univariate and multivariate conditional logistic regression were used to examine associations between traditional risk factors,CD36 variants and T2DM risk.Multiple logistic regression analysis was then used to examine the pair-wise interaction between CD36 polymorphisms and environmental factors on risk of T2DM,which was evaluated by using a likelihood ratio test.Classification and regression tree?CART?model was employed to explore the multi-factor interaction between CD36polymorphisms and environmental factors.Covariance analysis was used to evaluate the effect of CD36 variants on cardiometabolic risk indicators.Results1.A total of 1092 subjects?546 cases and 546 controls?were included in this study,with 195 males in each group.At baseline,the proportion of hypertension prevalence and family history of diabetes,the levels of body mass index?BMI?,waist circumference?WC?,fasting plasma glucose?FPG?,systolic blood pressure?SBP?,diastolic blood pressure?DBP?,total cholesterol?TC?,triglycerides?TG?and high-density lipoprotein cholesterol?HDL-C?were significantly different between cases and controls?P<0.05?.2.Univariate conditional logistic regression showed that general overweight/obesity,central obesity,family history of T2DM and hypertension had an increased risk of T2DM?P<0.05?.3.After adjusted for BMI,family history of T2DM and history of hypertension,multivariate conditional logistic regression showed that CD36 polymorphisms?rs3211956,rs2151916,rs7755 and rs1194197?were not associated with T2DM risk,assuming additive,dominant and recessive models of inheritance?P>0.05?.4.Unconditional logistic regression showed that there was interaction between rs7755 and general overweight/obesity(P _interaction=0.008);there was interaction also between rs7755 and central obesity(P _interaction=0.008).However,there was no interaction between rs3211956,rs2151916,rs7755,rs1194197 and history of hypertension(P _interaction>0.05).5.CART model was used to explore the multi-factor interaction between CD36polymorphisms and environmental factors,and then 6 explanatory variables were selected,including central obesity,general overweight/obesity,history of hypertension,rs1194197,rs2151916 and rs3211956.Comparing those without central obesity and history of hypertension,subjects with central obesity,general overweight/obesity,hypertension,rs1194197 and 2151916 variants,the risk of T2DM was increased?odds ratio=10.54,95%confidence interval:5.91-21.38?.6.Within the group of controls,covariance analysis showed that after adjusting for age,gender and BMI,rs2151916 polymorphism was associated with the level of TG?P=0.019?,and rs1194197 variant was related to SBP?P=0.023?.ConclusionsIn our study,we found no direct association between CD36 polymorphisms and the risk of T2DM.However,our results suggested the interaction of CD36 gene and environmental factors?such as obesity,hypertension?plays an important role in the progression of T2DM.Meanwhile,CD36 variants could influence the levels of TG and SBP.