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The association of C34T polymorphism of the AMPD1 gene with features of metabolic syndrome in patients with coronary artery disease without heart failure |
Krzysztof Safranow 1, Edyta Czyżycka 2, Agnieszka Bińczak-Kuleta 3, Ryszard Rzeuski 2, Katarzyna Jakubowska 1, Maria Olszewska 1, Janusz Skowronek 2, Andrzej Wojtarowicz 2, Andrzej B. Ciechanowicz 3, Zdzisława Kornacewicz-Jach 2, Dariusz Chlubek 1 |
1. Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstancow Wlkp. 72, Szczecin 70-111, Poland |
Abstract |
The common C34T polymorphism in the AMP deaminase-1 (AMPD1) gene results in premature stop codon, and thus, in a an inactive enzyme. Reduced activity of AMP deaminase may increase tissue concentrations of AMP and adenosine, a potent cardioprotective agent. There were reports of association of T34 allele with prolonged survival of patients with coronary artery disease (CAD) or heart failure (HF). It was also reported that variation in AMPD1 gene is associated with insulin clearance and may participate in syndromes of insulin resistance. The aim of the study was to investigate the associations between AMPD1 genotype and features of metabolic syndrome in patients with CAD without HF. Methods: 97 CAD patients were genotyped by PCR-RFLP. The PCR product (119 bp) of wild-type C34 allele was cleaved by Tai I into 98 bp and 21 bp fragments. The mutated T34 allele was identified by lack of Tai I restriction site. CAD was diagnosed on the basis of coronary angiography and patients with HF evidenced by clinical symptoms, echocardiography or high brain natriuretic peptide (BNP) plasma concentration were excluded from the study group. Results: AMPD1 C34T genotype frequencies were consistent with Hardy-Weinberg equilibrium: 68 (70%) CC, 23 (24%) CT and 6 (6%) TT. There were no significant differences between T allele carriers (CT+TT, n=29) and non-carriers (CC) regarding patients’ age, gender, CAD duration, ejection fraction and BNP concentration. T34 carriers had significantly lower body mass index (26.5 ± 2.7 vs 28.8 ± 4.7 kg/m2, p=0.026), waist circumference (89.5 ± 8.5 vs 98.2 ± 11.3 cm, p=0.00013) and waist-to-hip ratio (0.92 ± 0.08 vs 0.97 ± 0.08, p=0.0050). The prevalence of obesity (BMI≥30 kg/m2) was also lower in T34 carriers than in CC homozygotes (14% vs 37%, p=0.029). Fasting serum glucose concentrations were not significantly different between the genotype groups (101.3 ± 8.7 for CT+TT and 108.0 ± 19.0 mg/dL for CC, p=0.35), but the prevalence of diabetes and fasting serum glucose ≥126 mg/dL was significantly lower in T34 carriers (0% vs 16% and 0% vs 15%, respectively, both p=0.030). No significant differences between the genotype groups were found as regards the other features of the metabolic syndrome: hypertension and serum concentrations of HDL-cholesterol and triacylglycerols. The prevalence of metabolic syndrome was not significantly different between the T34 carriers and non-carriers, both when ATP III (2001) or IDF (2005) diagnostic criteria were used (21% vs 35%, p=0.23 and 45% vs 49%, p=0.83, respectively). Conclusions: Carriage of AMPD1 T34 mutated allele in CAD patients without HF is associated with lower prevalence of two features of metabolic syndrome: diabetes and obesity. The possible mechanisms of the association, including hypothetical changes in AMP-activated protein kinase activity, need further investigation. The study was supported by grant 2 P05B 079 26 from the Polish Committee for Scientific Research. |
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Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum B, by Krzysztof SafranowSee On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego Submitted: 2007-04-27 18:51 Revised: 2009-06-07 00:44 |