oa Molecular Diagnosis and Vaccines - Insulin receptor substrate-1 and transforming growth factor beta-1 gene polymorphisms in the metabolic syndrome
The metabolic syndrome (MS) encompasses a cluster of abnormalities including dysregulation of glucose and lipid metabolism, abdominal obesity and hypertension. This study aimed to investigate the association between insulin receptor substrate-1 (IRS-1) Glycine972Arginine (Gly972Arg) and transforming growth factor ?1 (TGF?1) Leucine10Proline (Leu10Pro) gene polymorphisms with MS and its different components. Fifty adult males with features of MS according to criteria set by the Adult Treatment Panel III (ATPIII) constituted the group of patients, 50 healthy males of comparable age served as controls. All participants were subjected to history taking, blood pressure, waist and hip circumference measurements. Laboratory investigations included fasting serum glucose, HbA1C, lipid profile, serum insulin and serum TGF?1. Insulin resistance was determined by the computer version of Homeostasis Model Assessment (HOMA2-IR). IRS-1 Gly972Arg polymorphism was determined by PCR / restriction digestion and TGF?1 Leu10Pro by the 5' nuclease assay. Compared to controls, MS patients were more obese, more insulin resistant and had an atherogenic lipid profile. Genotype distributions of both polymorphisms were not different between patients and controls. In MS patients, carriers of the IRS-1 mutant Arg972 allele were significantly more obese than non-carriers (p = 0.023), no other differences were detected. On the other hand, obese carriers of the Arg allele had significantly greater waist circumference, higher serum glucose, insulin, triglycerides and HOMA2-IR than non-carriers (p = 0.019, 0.03, 0.014, 0.02 and 0.01 respectively). Homozygous and heterozygous carriers of the mutant TGF?1 Pro 10 allele were more obese than Leu homozygotes (p = 0.012). Homozygous carriers of Pro10 had higher serum insulin, TGF?1 and HOMA2-IR than the other 2 genotypes (p = 0.0026, 0.0002 and 0.012 respectively). Waist circumference was an independent predictor of HOMA2-IR in patients. TGF?1 Pro 10 allele was more frequent in patients with than those without CHD (p = 0.023). HOMA2-IR was an independent predictor of CHD in MS patients. Our results indicate that, in the setting of MS, IRS-1 Arg972 and TGF?1 Pro10 variants are associated with obesity and insulin resistance. The TGF?1 Pro10 variant increases the risk of CHD. Understanding molecular mechanisms underlying such associations may help to plan treatment strategies to reduce health hazards related to MS.
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