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.
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.
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Authors: L Smiderle; M Fiegenbaum; M H Hutz; C R Van Der Sand; L C Van Der Sand; M E W Ferreira; R C Pires; S Almeida Journal: Pharmacogenomics J Date: 2015-08-25 Impact factor: 3.550
Authors: I Peter; A Kelley-Hedgepeth; G S Huggins; D E Housman; M E Mendelsohn; J A Vita; R S Vasan; D Levy; E J Benjamin; G F Mitchell Journal: J Hum Hypertens Date: 2009-02-05 Impact factor: 3.012