The Relationship of eNOS, p22 phox, CETP and ESR1 Gene Polymorphisms Related to Endocrine-Metabolic Parameters and Metabolic Syndrome in Postmenopausal Women - A Sample Population Based Study

Aims: To investigate the endocrine-metabolic changes in postmenopausal women with MetS and examine relationship with the polymorphisms of eNOS-G894T, p22(phox)-930 A/G, CETP TaqIB, ESR1 (PvuII and XbaI) genes.

Methods: 280 postmenopausal apparently healthy women aged between 60 and 80 years were classified into non-MetS (212) and MetS (68). Clinical, anthropometric and endocrine-metabolic parameters were measured. The single nucleotide polymorphisms were determined and tested for interacting with these parameters.

Results: The weight, waist circumference, blood pressure, WBC, triglycerides, LDL-C, TG/HDL-C ratio, apolipoprotein (apo)B, apoB/apoA-I ratio, fasting glucose, insulin, HOMA, uric acid, were higher and HDL-C was lower in MetS group thus fulfilled the criteria for the MetS. The significant higher levels of E2, T3, GHBP, PTH and lower levels of cortisol, SHBG, FSH, LH, IGFBP1, cortisol/DHEA ratio were also detected.

Genetic association studies showed that presence of A allele p22phoxA/G (OR=1.62; CI=1.08-2.42) and heterozygote AG-XbaI(ESR1) (OR=2.29; CI= 1.19-4.37) indicated a significant risk for MetS. The binary logistic regression (MetS vs Controls) showed an interaction of G894TeNOS polymorphism with MetS (OR>2.5; 95% CI =1.47-4.90) that associated with SBP, TG, apoB, uric acid, ASTGOT (OR>1) and HDL-C (OR<1). CETP TaqIB polymorphism associated with MetS (OR<1) in presence of SBP, GLU, TG with OR>1. ESR1 PvuII (T/C) associated with MetS (OR between 1.59-8.60) in presence of LDL-C, TG/HDL-C ratio, P with OD>1 and HDL-C, androstenedione, SHBG, FAI with OR<1.

In MetS group the carriers of -TT (eNOS-G894T) genotype had higher levels of blood pressure, glucose; -GG (p22phox A/G) had higher levels of BMI, apoB/apoA ratio; -B1B2 (CETP B1/B2) had higher levels of SBP, glucose, cholesterol, HDL-C, CRP, GHBP and lower levels of TSH; -CC (PvuII) and GG (XbaI) ESR1 genotypes showed higher levels of glucose.

Conclusions: These results sustain an interaction between the studied polymorphisms and the endocrine-metabolic changes in MetS pathogenesis.