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Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women

Second Department of Obstetrics and GynecologyAretaieio Hospital, University of Athens, 27, Themistokleous Street, Dionysos, GR-14578 Athens, Greece¹ Hormonal and Biochemical LaboratoryAretaieio Hospital, University of Athens, Athens, Greece² First Department of SurgeryUniversity of Athens Medical School, Laiko Hospital, Athens, Greece

(Correspondence should be addressed to I Lambrinoudaki; Email: ilambrinoudaki{at}hotmail.com)

Objective: To assess the association of genetic polymorphisms related to cardiovascular disease (CVD) risk with anthropometric parameters and indices of androgenicity in healthy postmenopausal women.

Design: Cross-sectional study in a University Menopause Clinic.

Methods: The following polymorphisms were assessed in 84 healthy postmenopausal women: glycoprotein IIIa Leu33Pro, apolipoprotein E2/E3/E4, methylenetetrahydrofolate reductase (MTHFR) Ala222Val, apolipoprotein B Arg3500Gln, paraoxonase 1 Gln192Arg, plasminogen activator inhibitor 1 4G/5G, cholesterol-7 -hydroxylase A-204C, and cholesterol ester transfer protein (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-β-estradiol, testosterone, sex hormone-binding globulin (SHBG), DHEA sulfate, -4-androstenedione (4A), free androgen index (FAI), free estrogen index (FEI), and homocysteine (Hcy). The anthropometric components were body mass index (BMI) and waist-to-hip ratio (WHR).

Results: MTHFR Ala222Val polymorphism was positively associated with testosterone, FAI, and FEI (P=0.001, P=0.0004, and P=0.014 respectively) and negatively with SHBG (P=0.047). Furthermore, women bearing this polymorphism had higher BMI and WHR compared with women with the wild-type variant (P=0.027 and P=0.044 respectively).

Conclusions: MTHFR Ala222Val polymorphism is associated with increased androgenicity and elevated BMI and WHR in healthy postmenopausal women. The significance of this association with respect to the CVD risk of postmenopausal women remains to be elucidated in future studies.