3.5 TCF7l2 Alleles and Risk of Type-2 Diabetes in Obese Hypertensive Patients Without Diabetes
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High Blood Press Cardiovasc Prev 2007; 14 (3): 145-196 1120-9879/07/0003-0145/$44.95/0 © 2007 Adis Data Information BV. All rights reserved.
Genetics and Pharmacogenomics 3.5 TCF7l2 Alleles and Risk of Type-2 Diabetes in Obese Hypertensive Patients Without Diabetes R. Sarzani, F. Pietrucci, F. Salvi, D. Caraceni, L. Lancioni, L. Mancinelli, B. Lorenzetti, F. Angelozzi, P. Dess`i-Fulgheri, A. Rappelli Department of Internal Medicine - University Politecnica delle Marche, Ancona, Italy Introduction: Obesity, that is increasing worldwide, has a causal role for both hypertension and type 2 diabetes mellitus (DM2). Moreover, obesity and hypertension are independently associated with an increased risk of developing DM2. A recent landmark study described the association among three markers (“X allele” of the DG10S478 microsatellite and T alleles of the rs12255372 and rs7903146 SNPs) of TCF7L2 gene and DM2 in three different populations; this association was then confirmed in all subsequent studies. These genetic markers could be especially useful to identify patients at risk of developing DM2 in a population that is already at high risk (both metabolic and cardiovascular), such as the obese hypertensive patients. Obese hypertensive patients with the TCF7L2 risk-associated alleles might require more aggressive measures in order to prevent new-onset DM2. So, the aims of the study were: 1) to identify carriers of the X allele of the microsatellite DG10S478 in a obese hypertensive population without diabetes; 2) to compare X allele prevalence with a control population. Methods: We studied 204 obese hypertensive patients (BMI 34.5±4.3 kg/m2; SBP 151±19.9 mmHg; DBP 94.3±12.4 mmHg on therapy; age 100 mg/dl, diabetes was excluded by an oral glucose test) and 222 unselected subjects coming from the same geographic region, as control population. Microsatellite genotyping were performed by PCR and direct sequencing from genomic DNA. Results: The X allele, that increase the risk to develop diabetes, had a frequency (35.4%) similar to that observed in populations studied previously. There was no difference in both allele and genotype distribution between obese hypertensive and control population (X allele 36.8% vs. 34.5%, p=0.68). Considering X allele as dominant, obese hypertensive patients carrying this allele showed higher BMI and glycaemia (p=0.023 and p=0.042, respectively). Moreover, patients with metabolic syndrome (MS) had a higher frequency of X allele than obese hypertensives without MS (66.2% vs. 40%, p=0.006). Conclusions: The X allele of the DG10S478 microsatellite of TCF7L2 gene may be useful in identifying obese hypertensive patients at higher risk of developing diabetes: although its frequency is not increased, when X allele is present, these patients show higher BMI and glycaemia. Moreover, X allele, acting through beta pancreatic cells dysfunction coupled with higher BMI, predisposes obese hypertensive patients to the MS.
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