Metabolic Syndrome in Postmenopause: eNOS, p22 phox, CETP and ESR1 Gene Polymorphisms Related to Endocrine-Metabolic Changes

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. Our results sustain an interaction between the
studied polymorphisms and their phenotypes in conferring a higher susceptibility to the endocrinemetabolic
changes involved in pathogenesis of MetS. The elevated values of TG/HDL-C and
apoB/apoA ratios could be risk indicators for calculation cardiovascular risk in of MetS.