Influence of the High Mobility Group A1 genetic polymorphism on indices of metabolic syndrome and insulin resistance in the Iraqi population: Case-control study

ABSTRACT: The high mobility group A1 gene (HMGA1) rs139876191 variant has been related to metabolic syndrome and type 2 diabetes, but data are lacking in Middle Eastern populations. The study aimed to assess whether the HMGA1 rs139876191 variant is associated with metabolic syndrome risk and whether this variant predicts the risk of insulin resistance. This case-control study was carried out at single center in Kirkuk city/ Iraq from February to August 2022. Polymorphisms in HMGA1 and genotyping were identified by Sanger sequencing of genomic DNA obtained from 91 Iraqi participants (61 patients with metabolic syndrome and 30 control). Lipid profile, serum (glucose and insulin), glycated hemoglobin, blood pressure, body mass index, and waist circumference were also measured. The high prevalence of the del/del genotype of rs139876191 was found. Minor allele frequency of rs139876191 was (0.16) in both metabolic syndrome and the control group. A non-significant difference in genotyping was identified between total metabolic syndrome and the control group. The del/ins variant was associated with significantly higher waist circumference, triglyceride(TG), low-density lipoprotein(LDL), very low-density lipoprotein(VLDL), and glycated hemoglobin(HbA1c) (P=0.03, 0.041, 0.007, 0.034, and 0.001 respectively), and with significantly lower high-density lipoprotein(HDL) (p=0.000). Linear regression analysis showed no significant effect of the variant (del/ins) on developing insulin resistance. Thus, rs139876191 polymorphism with del/ins genotype in the HMGA1 gene was not associated with metabolic syndrome risk but it was associated with indices of metabolic syndrome including waist circumference, TG, HDL, LDL, VLDL, and HbA1c. Besides, this variant did not predict the risk of insulin resistance.