Association of ABCA1 R219K and C69T single nucleotide polymorphisms with type 2 diabetes mellitus: A case control study

Abstract

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder associated with alterations in the metabolism of carbohydrates, proteins and lipids. ATP binding cassette transporter 1 (ABCA1) encoding the ABCA1 protein plays a critical role in the reverse cholesterol transport of high‑density lipoprotein-cholesterol (HDL-c) metabolism. ABCA1 gene single nucleotide polymorphisms (SNPs) have been found to be associated with abnormalities in the serum levels of HDL‑c, thereby disrupting the cholesterol removing ability of cells. The aim of the present study was to determine the association between the R219K and C69T SNPs of ABCA1 gene variants and T2DM. For this purpose, a case control study was conducted among 50 patients with T2DM who were selected as cases, and 50 age‑ and sex‑matched patients without comorbidities were selected as the controls. Venous blood samples were collected from all participants following overnight fasting. Plasma glucose, glycated hemoglobin (HbA1c) and lipid profile estimations were performed using an autoanalyzer with standard methods. ABCA1 gene polymorphisms were determined using the polymerase chain reaction‑restriction fragment length polymorphism method. The body mass index for both the case and control groups was found to be above the revised cut‑off value for obesity. HDL‑c levels were below the optimum level in the case and control group. The distribution of genotype and dominant alleles of the C69T and R219K SNPs of the ABCA1 gene did not differ significantly between the case and control groups. The present study suggests the existence of a defective ABCA1 genotype in the studied population, predisposing these individuals to a decrease in serum HDL‑c levels. This interferes with cholesterol sequestration from foam cells and creates an inflammatory state, which is aggravated by obesity. Thus, HDL‑c becomes dysfunctional from inflammation‑mediated structural modifications and paves the way for atherogenic dyslipidemia associated with T2DM.