Abstract :Peroxisome proliferator-activated receptor-gamma2 (PPAR-?2), a member of nuclear receptor super family, has a key role in the regulation of adipocyte differentiation, lipid and carbohydrates metabolism.
The aim of the present study was to determine whether the Pro12Ala polymorphism of PPARg2 gene affects the acute forms of coronary heart disease (CHD) in Russian population. The second aim of this study was to identify the association of Pro12Ala polymorphism of PPARg2 gene with insulin resistance.
In the current study 278 patients aged 36 to 78 years (232 male and 46 female) with verified diagnosis of coronary heart disease were enrolled. The comparison group consisted of 220 subjects without CHD of comparable age (mean age - 60, 09 ± 0, 72 years). The identification of polymorphic variants of Pro12Ala polymorphism of PPAR-g2 gene based on the method of polymerase chain reaction (PCR) followed by restriction analysis. Serum immunoreactive insulin level was revealed by ELISA (DRG Diagnostics, Germany), HOMA index of insulin resistance was calculated.
The frequency of 12Ala allele in CHD patients was higher than in the control group (0.15 and 0.08 respectively, p=0.0003). 12Ala allele carriage was associated with increased risk of CHD (OR=2, 00, ?=0, 0006). No significant differences in Pro12Pro and Pro12Ala + Ala12Ala genotype distribution in CHD patients with or without obesity, smoking factor, family history were revealed. Pro12Ala and Ala12Ala genotypes detected significantly more often in patients with myocardial infarction at a young age (45 years and younger). Carriage of Ala12 allele was associated with an increased risk of myocardial infarction at a young age to 2.49 times (p<0, 05).
In CHD patients with diabetes Ala allele detected significantly more rare, than in CHD patients with diabetes – non Ala allele carriers (in 17% and 30% of cases, p=0, 01). 12Ala allele carriage was associated with diminished risk of diabetes type 2. Serum immunoreactive insulin level was lower in the group of CHD patients – 12Ala allele carriers, than in patients with Pro12Pro genotype (11, 06±1, 12 µU/ml and 21, 02±1, 97 µU/ml respectively, ?=0,008). The same tendency was revealed in HOMA index assessment.
Conclusion: The study has demonstrated that Ala12 PPAR ? allelic variant influence the predisposition for CHD in human subjects and was associated with the risk of myocardial infarction at the age 45 years and younger in the population of North-West region of Russian Federation. 12Ala allele carriage is associated with reduced risk of type 2 diabetes in CHD patients and with lower content of immunoreactive insulin and HOMA index.