Sex-specific association between estrogen receptor-alpha gene variation and measures of adiposity: the Framingham Heart Study.
BACKGROUND
Polymorphisms in estrogen receptor-alpha (ESR1) may be associated with variation in body mass index and waist circumference. However, most prior studies have been limited by sample size and power.


METHODS
DNA from 1763 unrelated men and women (mean age, 56 yr) from the Framingham Heart Study offspring cohort was genotyped for four ESR1 polymorphisms: T30C (rs2077647) in exon 1, PvuII (rs2234693), and XbaI (rs 9340799) in intron 1, and C1335G (rs 1801132) in exon 4.


RESULTS
Men homozygous for the PvuII C allele (frequency, 0.45) had lower waist circumference (99.3 cm), compared with TT homozygous men (99.8 cm) and heterozygotes (100.6 cm) (P < 0.004). Similar results were obtained with XbaI, which lies in the same linkage disequilibrium block. C1335G also demonstrated a gender-specific association: men with CG or GG genotypes had lower mean body mass index, 27.7 and 27.9 kg/m2 respectively, compared with 28.6 kg/m2 among the CC homozygotes (P < 0.01). No significant associations were seen with T30C, nor were associations observed among women.


CONCLUSIONS
Polymorphisms in ESR1 are associated with measures of adiposity in men. These associations further support the hypothesis that the intron 1 region of ESR1 influences phenotypes important for cardiovascular risk.
Fox
Caroline S
CS
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702, USA. foxca@nhlbi.nih.gov
Yang
Qiong
Q
Cupples
L Adrienne
LA
Guo
Chao-Yu
CY
Atwood
Larry D
LD
Murabito
Joanne M
JM
Levy
Daniel
D
Mendelsohn
Michael E
ME
Housman
David E
DE
Shearman
Amanda M
AM
D050154:Adiposity; D000328:Adult; D015992:Body Mass Index; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012737:Sex Factors; D049629:Waist-Hip Ratio
D047628:Estrogen Receptor alpha