Gender Differences of Gly972Arg Polymorphism of the IRS-1 Gene Related to Cardiovascular Disease Risk Factors Among Indonesians
Background: Cardiovascular disease is driven by traditional risk factors, sex, and genetic differences. The Asian population, specifically Indonesians, has been known at high risk of insulin resistance and endothelial dysfunction. A possible genetic risk factor related to cardiovascular diseases is Gly972Arg polymorphism of insulin receptor substrate 1 (IRS-1) gene, as this impairs endothelial function. To date, whether there is a gender difference in Gly972Arg polymorphism of the IRS-1 gene in Indonesians is unknown. This study aimed to to define whether there is a gender difference in Gly972Arg polymorphism of the IRS-1 gene in Indonesians. Methods: We studied adults living in two areas (rural and urban) in Indonesia. We collected demographic and clinical data from the study subjects. Gly972Arg polymorphism of the IRS-1 gene (rs1801278) was detected using TaqMan real-time polymerase chain reaction. Results: A total of 378 subjects were recruited. The wild-type allele (CC) was found in 86 (22.8%) subjects, heterozygous mutant allele (CT) in 245 (64.8%), and homozygous mutant allele in 47 (12.4%). The proportion of subjects with T alleles was significantly higher among women than men (54.6% vs. 45.4%, odds ratio: 1.89; p = 0.01). Subjects with T allele more often have hypertension (odds ratio: 1.69, p = 0.058). Conclusion: There were a higher proportion of women than men carrying the T allele of Gly972Arg polymorphism among Indonesians. Individuals with the T allele appeared to show a greater prevalence of hypertension. These results may explain a possible mechanism of the high prevalence of metabolic syndrome in Indonesia, especially in women.
Ranasinghe P, Mathangasinghe Y, Jayawardena R, Hills AP, Misra A. Prevalence and trends of metabolic syndrome among adults in the Asia-pacific region: A systematic review. BMC Public Health 2017;17:1–9
Lin CF, Chang YH, Chien SC, Lin YH, Yeh HY. Epidemiology of dyslipidemia in the Asia Pacific Region. Int J Gerontol. 2018;12:2–6.
Chan JCN, Malik V, Jia W, et al. Diabetes in Asia. Lancet. 2010;375:408–18.
Yousef A, Behiry E, Abd Allah W, et al. IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance. Appl Clin Genet. 2018;11:99–106.
McGettrick AJ, Feener EP, Kahn RR. Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. J Biol Chem. 2005;280:6441–6.
Baroni MG, D’Andrea MP, Montali A, et al. A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol. 1999;19:2975–80.
Hribal ML, Federici M, Porzio O, et al. The Gly→Arg972 amino acid polymorphism in insulin receptor substrate-1 affects glucose metabolism in skeletal muscle cells. J Clin Endocrinol Metab. 2000;85:2004–13.
Wulandari P, Sukmawan R, Sunu I, Supari SF. Relationship between Gly972Arg Variant of Insulin Receptor Substrate-1 Gene and Endothelial Dysfunction Measured by Flow Mediated Dilation. Eur Hear J Suppl 2018;20(suppl_D):D21–D34.
Syahrul, Wibowo S, Haryana SM, Astuti I, Nurwidya F. The role of insulin receptor substrate 1 gene polymorphism Gly972Arg as a risk factor for ischemic stroke among Indonesian subjects. BMC Res Notes. 2018;11:1–5.
Galiuto L, Locorotondo G. Gender differences in cardiovascular disease. J Integr Cardiol. 2015;1:20–2.
Widmer RJ, Lerman A. Endothelial dysfunction and cardiovascular disease. Glob Cardiol Sci Pract. 2014;43:291–308.
Perticone F, Sciacqua A, Scozzafava A, et al. Impaired endothelial function in never-treated hypertensive subjects carrying the Arg972 polymorphism in the insulin receptor substrate-1 gene. J Clin Endocrinol Metab. 2004;89:3606–9.
Villuendas G, Botella-Carretero JI, Roldán B, Sancho J, Escobar-Morreale HF, San Millán JL. Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. Hum Reprod. 2005;20:3184–91.
Kim JA, Montagnani M, Chandrasekran S, Quon MJ. Role of lipotoxicity in endothelial dysfunction. Heart Fail Clin. 2012;8:589–607.
Kilpeläinen TO, Zillikens MC, Stan A, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet. 2012;43:753–60.
Tan NC, Koh KH, Goh CC, Koh YLE, Goh SCP. Asian patients with dyslipidemia in an urban population: Effect of ethnicity on their LDL-cholesterol treatment goals. J Clin Lipidol. 2016;10:410–9.
Hatma RD. Lipid profiles among diverse ethnic groups in Indonesia. Acta Med Indones. 2011;43:4–11.
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