The Role Of LRP5Polymorphisms, Environmental Factors, And Gene-environmental Interaction In The Development Of Type2Diabetes Mellitus

Type2diabetes mellitus (T2DM) ischaracterized by impaired insulinsecretion,insulin resistance and hyperglycemia. Long-term chronic hyperglycemia oftenleadsto multiple organ dysfunction and tissue structure abnormalities, which would pose aserious threat to the safety and quality of life for patients. As a complex disorder,T2DMis caused by both genetic and environmental factors. WNTsignalingpathwayinduced differentiation and apoptosis of islet cell, as well as insulinsecretion, whichplays an important role in the development of T2DM.As theco-receptorof WNTsignaling pathway, LRP5proteincombined with WNT ligandsand Frizzled receptors and initiated the canonical WNT signaling pathways, whichmay be associated with T2DM.ObjectiveThe purpose of this study is to investigate the association of LRP5variants,environmental risk factors,andgene-environment interactions withT2DM.MethodsCase-control study design was used for this study. The questionnaire interview(demographic characteristics, medical history, and behavior riskfactors),anthropometricmeasurements (height, weight, waist circumferences [WC],and blood pressure [BP]) and laboratory measurements (fasting plasma glucose[FPG], total cholesterol [TC], triglyceride [TG], high-density lipoprotein cholesterol[HDL-C], low-density lipoprotein cholesterol [LDL-C]) were done for the studyparticipants. Genomic DNA was extracted from whole blood, PCR-RFLP was usedto detect the genotype. ResultsA total of9619persons (1842cases and7777controls) were selected andcompleted the study.Univariate analysis indicated thatmoderate physical activity(OR=0.234,95%CI=0.199–0.276) andheavyphysical activity (OR=0.185,95%CI=0.164–0.209)were the protective factors for the T2DM.Overweight(OR=2.647,95%CI=2.309–3.034), general obesity(OR=9.073,95%CI=7.874–10.456),central obesity(OR=4.406,95%CI=3.896–4.983),hypertension(OR=2.233,95%CI=2.015–2.476), TC≥5.18mmol/L(OR=4.276,95%CI=3.520–5.194), TG≥1.70mmol/L(OR=2.462,95%CI=2.194–2.762), HDL-C<1.04mmol/L(OR=1.235,95%CI=1.111–1.373), and LDL-C≥4.14mmol/L(OR=4.347,95%CI=3.432–5.505)were the risk factors for the T2DM.Aftercontrolling for potential confounders, moderate physical activity (OR=0.265,95%CI=0.221–0.318) and heavyphysical activity(OR=0.207,95%CI=0.181–0.237)were the protective factors for the T2DM.Overweight(OR=1.735,95%CI=1.441–2.090), general obesity(OR=5.818,95%CI=4.739–7.143),central obesity(OR=1.793,95%CI=1.492–2.156),hypertension(OR=1.379,95%CI=1.217–1.563), TG≥1.70mmol/L(OR=1.544,95%CI=1.336–1.784), and LDL-C≥4.14mmol/L(OR=2.473,95%CI=1.681–3.639)were the risk factors for the T2DM.LRP5gene rs11228303variantswas not associated with T2DM underdominantmodel, recessive model, and additive model,even after controlling for covariates(all P>0.05).There was no statistically significant differencesbetween CC and CT+TTgenotype of metabolic characters(all P>0.05). The interaction between rs11228303variants and environmental risk factors were not associated with the risk of T2DM incurrent study (all P>0.05).Conclusions1. In current study participants, moderate and heavy physical activity were theprotective factors of T2DM, overweight, general obesity, central obesity,hypertension, TG≥1.70mmol/L, and LDL-C≥4.14mmol/L were the risk factors of T2DM.2.LRP5gene rs11228303variants and it’s interaction with environmental riskfactors were not associated with the risk of T2DM in this study population.