Abstract P235: Association of Lipid Related Genetic Variants and Hypertriglyceridemia in Type 2 Diabetic Patients from a Chinese Population

Abstract

Previous studies have showed that hypertriglyceridemia may be a stronger risk factor for coronary heart disease in diabetic patients than non-diabetic individuals. Multiple genomic loci have been identified to be associated with lipid levels among general populations by genome-wide association studies. It is unclear about their effects on lipid levels among type 2 diabetes (T2D) patients. The present study aimed to investigate the associations of lipid related genomic loci and hypertriglyceridemia (defined as triglycerides ≥ 1.70mmol/L or taking lipid-lowering medications) among 5,338 T2D patients from China. We genotyped 9 single nucleotide polymorphisms (SNPs) within or near ABCA1 , DOCK7 , TOMM40 , GCKR , HNF1A , HNF4A , LDLR , BAZ1B and BUD13 genes. Under an additive genetic model, logistic and linear regression models were used to examine the associations of these genomic loci with hypertriglyceridemia and the triglycerides level (among 4,908 individuals without taking any lipid-lowering medications) with adjustment for age, sex, and body mass index, respectively. Five SNPs near ABCA1 (rs3890182), TOMM40 (rs157580), GCKR (rs780094), BAZ1B (rs2240466) and BUD13 (rs28927680) genes were significantly associated with hypertriglyceridemia among T2D patients (OR [95% CI] = 0.79 [0.67, 0.93] for per A allele of rs3890182, P = 4.03х10 -3 ; 1.13 [1.04, 1.22] for per A allele of rs157580, P = 2.81х10 -3 ; 0.87 [0.80, 0.94] for per G allele of rs780094, P = 4.26х10 -4 ; 0.77 [0.68, 0.87] for per T allele of rs2240466, P = 1.28х10 -5 ; 3.83 [1.39, 10.50] for per C allele of rs28927680, P = 9.27х10 -3 ). Six SNPs within or near ABCA1 , GCKR , BAZ1B , TOMM40 , HNF1A and LDLR were significantly associated with the triglycerides level. For example, minor alleles of GCKR and BAZ1B were associated with lower triglycerides level (β [SE] = -0.025 [0.005] for per G allele of rs780094, P = 7.88х10 -7 ; -0.035 [0.007] for per T allele of rs2240466, P = 2.03х10 -6 ). To test the robustness of these findings, we conducted a sensitivity analysis to only include newly diagnosed T2D patients (2,646 out of 4,908 patients without taking any lipid-lowering medications). The associations between ABCA1, TOMM40 , GCKR and BAZ1B with hypertriglyceridemia maintained significant ( P value ranged from 7.79х10 -4 to 1.29х10 -2 ), as well as their associations with the triglycerides level ( P value ranged from 2.76х10 -5 to 2.89х10 -2 ). In conclusion, our study provides the first data for the effects of lipid-related genomic loci on hypertriglyceridemia and the triglycerides level among T2D patients of the Chinese population. Further studies were warranted to replicate these findings.