Association of polymorphisms in the estrogen receptor α gene with body fat distribution

Objective: To examine whether polymorphisms of the estrogen receptor (ER) alpha gene are associated with body fat distribution. Design: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T-->C (PvuII) and an A-->G ( XbaI), in the first intron of the ERalpha gene. Subjects: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40-79 y). Measurements: The ERalpha genotypes (by automated fluorescent allele-specific DNA primer assay system), anthropometric variables, fat mass (FM) and percentage FM (%FM) (by dual-energy X-ray absorptiometry). Results: FM and waist were inversely associated with age (r=-0.630 and -0.504, respectively) in women with the GG genotype. On the other hand, waist circumference of the AA genotype was positively correlated with age (r=0.231). Thus, for middle-aged women (40-59 y) with the AG or GG genotype body mass index (BMI), %FM, FM, waist, hip and waist-to-hip ratio (WHR) were larger than those with the AA genotype. In particular, FM and waist were greater by 20% and 9%, respectively, for the GG genotype, compared to the AA genotype. Alternatively, FM and waist were smaller by 18% and 6%, respectively, in older women with the GG genotype, compared to the AA genotype. No effect was found among the A-->G polymorphisms for men. For both genders, no difference was found in any variables among the TT, TC and CC genotypes with the exception of BMI of older men (60-79 y). Conclusion: No association was found between the ERalpha gene polymorphisms and body fat distribution in men. For women, the A-->G polymorphism, in particular the GG genotype, may contribute to the development of upper-body obesity in middle-aged individuals, but may serve to decrease the whole-body and abdominal fat tissue of older individuals.