IMMUNE AND METABOLIC DISORDERS IN HYPERTENSION, OBESITY, AND HEPATIC STEATOSIS ASSOCIATE WITH PPAR-GAMMA2 PRO12ALA AND ACE I/D GENES’ POLYMORPHISMS

Abstract

Objective: Metabolic changes and obesity play important roles in arterial hypertension pathogenesis and progression. Whereas hepatic steatosis (HS) and AH have multiple common mechanisms of development involving metabolic and immune changes, the aim of study was to investigate the influence of Pro12Ala polymorphism of PPAR-↖2 gene and I/D polymorphism of ACE gene on metabolic profile and cytokines in obese patients with HS and AH. Design and method: Study involved 154 AH patients with HS (87 males, 67 females, age 50.06±7.34). Duration of HS 1-5 years, AH 3-21 years. Metabolic disorders were defined with body mass index (BMI), glycaemia, immunoreactive insulin (IRI), total cholesterol (TC), low and high density cholesterol (LDL-C, HDL-C), triglycerides (TG), C-peptide (CP) levels and HOMA-IR index. TNF- ↑ and leptin plasma levels were assessed by ELISA. Genes’ polymorphism of PPAR-↖2 (Pro12Ala), and ACE (I/D) alone or in combination was studied with PCR. Results: Differences of BMI, plasma glucose, IRI, HOMA-IR, CP and leptin are independent from ACE gene genotypes (p>.05). Pro-allele carriers of PPAR-↖2 gene have higher BMI than AlaAla carriers (32.7±2.1 and 27.9±1.1 kg/m2 vs 25.6±0.8 kg/m2, accordingly (p<.05), leptin level – 14.3±0.41 and 8.6±0.25 ng/ml vs 3.7±0.22 ng/ml, (p<.001), glucose level – to 10.2% and 10.9% accordingly (p<.05); CP level was higher in ProPro-genotype than in Ala-allele carriers to 15.7% (p<.05). Risk group of dyslipidemia are ProPro-genotype carriers of PPAR-↖2 gene with higher level of TC, TG and LDL-C to 16.4%, 17.3% and 27.9% (p<.05) and lower level of HDL-C in women to 25.6% (p = .038). Lipids levels are independent on ACE I/D polymorphism. Baseline TNF-↑ plasma levels did not significantly deviate between genotypes of PPAR-↖2 gene, but D-allele carriers (I/D+DD) of ACE gene had higher baseline TNF-↑ plasma levels (91.61 and 109.11 pg/ml, accordingly p<.01). Conclusions: In HS hypertensive patients metabolic disorders are clearly associated with PPAR-↖2 Pro-allele (carbohydrates) and ProPro-genotype (lipids). Presence of D-allele of ACE gene is associated with reliably higher level of TNF-↑ plasma levels.