rs7903146 polymorphism at transcription factor 7 like 2 gene is associated with total cholesterol and lipoprotein profile in HIV/hepatitis C virus-coinfected patients

Abstract

Transcription factor 7 like 2 (TCF7L2) rs7903146 polymorphism has been associated with metabolic disturbance and cardiovascular disease. The aim of this study was to analyze the association between TCF7L2 rs7903146 polymorphism and potential disturbances on the lipid profile in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We performed a cross-sectional study on 263 HIV/HVC-coinfected patients. TCF7L2 polymorphism was genotyped by GoldenGate assay. The analysis was performed by linear and logistic regression under a dominant model of inheritance. The variables analyzed were total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), non-HDL-C, and triglycerides. Patients harboring the rs7903146 TT/TC genotype showed a diminished concentration of TC (p=0.003), LDL-C (p=0.004), HDL-C (p=0.012), and non-HDL-C (p=0.013), a lower percentage of TC≥200 mg/dl (p=0.038), and a higher percentage of HDL≤40 mg/dl (p=0.023). In addition, we observed that rs7903146 was differently related to fasting serum lipid levels according to the HCV-genotype (HCV-GT). With regard to HCV-GT1 patients, the rs7903146 TT/TC genotype was associated with lower levels of HDL-C [adjusted arithmetic mean ratio (aAMR)=0.91; p=0.049] and an elevated percentage of patients with HDL-C≤40 mg/dl [adjusted odds ratio (aOR)=3.26; p=0.003]. For HCV-GT3 patients, the rs7903146 TT/TC genotype was associated with lower serum values of TC (aAMR=0.81; p=0.037), LDL-C (aAMR=0.67; p=0.001), and non-HDL-C (aAMR=0.75; p=0.002) and a reduced percentage of TC≥200 mg/dl (aOR=0.089; p=0.037). In conclusion, the TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of TC, LDL, and HDL in HCV-GT3 patients, and lower levels of HDL-C in HCV-GT1 patients, suggesting a role in cardiovascular disease and a potential use as a biomarker in HIV/HCV-coinfected patients.