Background Type 2 diabetes (T2D) affects over 15 million Americans, and the prevalence is rising precipitously. T2D patients are at risk for atherosclerosis and microvascular complications; identifying those at risk can lead to improved outcomes. Risk for complications due to dyslipidemia is modulated by genetic factors. Common variations in the microsomal triglyceride transfer protein (MTP −493G/T) and apolipoprotein B (apoB insertion/deletion [In/Del]) genes may modulate the risk for diabetic complications through their impact on lipid metabolism.
Methods As part of a longitudinal case-control study of T2D in a French population (401 cases, 113 controls, mean age 59.5 years at baseline, and 4.2-year mean follow-up) we examined the relationship between MTP −493G/T, apoB In/Del, lipoprotein parameters, and the prevalence of diabetic complications.
Results After adjusting for relevant covariates, MTP −493G/T was associated with T2D (p = .032), lower apoB concentrations (p = .024), triglycerides (p = .047), total cholesterol (p = .049), body mass index (p = .006), and creatinine levels (p = .007). Given the biochemical interaction of apoB and MTP proteins in the assembly of triglyceride-rich lipoproteins, we tested for their genetic interaction as a predictor of apoB concentration; T2D individuals with MTP T/T and apoB In/In had the highest apoB concentrations (p = .05). MTP −493G/T was associated with nephropathy at follow-up (p = .048), with G-allele homozygotes more likely to have nephropathy than T-allele carriers (odds ratio = 1.621, 95% confidence interval 1.004, 2.616).
Conclusion MTP −493G/T is associated with T2D and impacts lipoprotein parameters associated with complications in T2D. Importantly, we contribute novel evidence that lipoprotein metabolism genes are risk factors for diabetic complications.
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