Insulin-like growth factor-I gene poly-morphisms and left ventricular function in Turkish obese women with insulin resistance.

I growth factor I (IGF-I) is a peptide which is involved in the regulation of glucose hemostasis, stimulates bone growth, cell differentiation, and metabolism. Obesity may cause structural and functional changes in the heart even in the absence of hypertension and organic heart disease. The IGF-I may play an important role in the development of cardiovascular diseases.1 Due to the interference of IGF-binding proteins, measuring circulating IGF-I levels may be misleading in reflecting the IGF-I bioactivity in diseased conditions. The polymorphism in the promoter region of the IGF-I gene may directly influence the expression of IGF-I. This polymorphism can be used to determine subjects with a genetic predisposition toward chronic low exposure of IGF-I in the cardiovascular system. Studying this polymorphism in relation to obesity and subclinical cardiac involvement may better reflect the effects of long term IGF-I exposure on cardiovascular system. We have recently demonstrated that obesity is associated with low IGF-I levels, and the most frequent IGF-I gene polymorphism allele is longer than 194 base pair (bp) in both obese insulin resistant patients and controls, and the cause of lower IGF-I levels in obese patients may not be the IGF-I gene polymorphism and it may be insulin resistance (IR).2 Tissue Doppler imaging has enhanced our capacity to identify early abnormalities in systolic and diastolic ventricular function. The objective of the study was to investigate the association between the IGF-I promoter polymorphism, and the occurrence of left ventricular subclinical involvement on echocardiogram of obese women with IR. The study was carried out prospectively at the Cardiology, Endocrinology, and Medicine Outpatient Clinics of Pamukkale University, Denizli, Turkey from March to July 2009. The study was approved by the institution’s Medical Ethics Review Committee. The study was conducted according to the principles of Helsinki Declaration. Patients were included in the study if they were obese women with IR. A total of 64 patients were included in the present study (34 obese women with IR, mean age 45.6 ± 11.9 and 30 agematched healthy women). Individuals with smoking history, ethanol consumption (more than 60 g, 0.5 liters wine/d), diabetes mellitus, acromegaly, growth hormone deficiency, cardiac and/or ischemic cerebrovascular disease, thyroid dysfunction, hepatic insufficiency, impaired renal function, malnutrition, and other major pathologies were excluded. None of the study subjects were taking any medications, which might influence glucose, insulin metabolism, or secretion. Anthropometric measurements were obtained, such as body mass index (BMI), waist circumference, and waistto-hip ratio (WHR)). A BMI >30 kg/m2 was regarded as obesity. Routine biochemical values, insulin levels, thyroid function tests, IGF-1, GH (growth hormone), and IGFBP-3 (IGF binding protein) levels were examined. Polymorphisms in the promotor region of the IGF-1 gene consist of a highly polymorphic microsatellite composed of variable cytosine adenosine (CA) repeats. The number of CA repeats ranges between 10 and 24, with the most common allele containing 19 CA repeats (192 bp allele). Genomic DNA from the study subjects and controls were isolated. Interested genomic areas were studied using specific primers by polymerase chain reaction methods. Separation of amplified fragments was carried out by agarose gel electrophoresis. Amplified fragments were identified by using the ultraviolet gel documentation system. Genotyping of the 192 bp IGF-I promoter polymorphism resulted in 3 possible genotypes: shorter than192 bp allele, 192-194 bp allele, and longer than 194 bp. Standard and pulsed Doppler tissue echocardiograms were obtained in all participants using a Vivid 7 ultrasound machine (GE Vingmed, Milwaukee, Wisconsin, USA) with a 2.5-MHz phased array probe. Values are expressed as mean ± standard deviation. Data were analyzed using Statistical Package for Social Sciences version 15 (SPSS Inc., Chicago, IL, USA). Comparisons between obese women with IR and controls were performed by Mann-Whitney U test. Multiple genotype groups were analyzed by KruskalWallis test. A p<0.05 was considered significant. The 2 groups had similar mean ages however, the BMI, waist circumferences, fasting plasma glucose, fasting insulin, homeostatic model assessment (HOMA)IR were markedly increased in obese women with IR as expected (p=0.000). The IGF and GH were markedly decreased in obese women with IR (p=0.005). Sixty six percent of obese women, and 93.5% of controls had longer than 194 bp IGF-I promoter polymorphism. Heart rate, left ventricle (LV) end-diastolic diameter, LV end-systolic diameter, interventricular septum, LV ejection fraction, the peak annular velocity during atrial contraction from the lateral wall, the peak annular