Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene with postmenopausal osteoporosis

• Published in: Osteoporosis international Vol. 12; no. 12; pp. 1015 - 1019
• Main Authors: Ongphiphadhanakul, B, Chanprasertyothin, S, Payattikul, P, Saetung, S, Piaseu, N, Chailurkit, L, Rajatanavin, R
• Format: Journal Article
• Language: English
• Published: England 01.12.2001
• Subjects: Aged; Bone Density - genetics; Estradiol - blood; Estrogen Receptor alpha; Exons; Female; Femur Neck - physiopathology; Genetic Predisposition to Disease; Genotype; Humans; Logistic Models; Middle Aged; Osteoporosis, Postmenopausal - blood; Osteoporosis, Postmenopausal - genetics; Polymorphism, Single Nucleotide; Receptors, Estrogen - genetics
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s001980170010

We report the association of a newly identified synonymous G2014A single nucleotide polymorphism (SNP) which does not alter the amino acid sequence in exon 8 of the estrogen receptor-alpha (ERalpha) gene with osteoporosis in Thai postmenopausal women. Subjects consisted of 228 postmenopausal women aged more than 55 years divided into two groups--with vertebral or femoral osteoporosis (n = 106) or without osteoporosis (n = 122)--according to bone mineral density (BMD) criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the end of the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and 95% CI. The allele frequency of the G2014A polymorphism was 26.4% in osteoporotic subjects and was significantly higher than that in non-osteoporotic women (15.2%) (p<0.05). By stepwise logistic regression analysis, it was found that the G2014A polymorphism was related to the presence of osteoporosis (odds ratio 2.7 per A allele, 95% CI 1.49-4.76) independently of body weight (odds ratio 0.93 per kg, 95% CI 0.89-0.96) and years since menopause (odds ratio 1.12 per year, 95% CI 1.08-1.19). In a multiple linear regression model, L2-L4 BMD of osteoporotic subjects was associated with body weight (p<0.05), endogenous estradiol levels (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We conclude that a G2014A SNP in exon 8 of ERalpha is associated with the presence and severity of postmenopausal osteoporosis. Linkage disequilibrium between this polymorphism and the 3'-untranslated region of the ERalpha gene which may participate in the regulation of ERalpha gene expression remains to be determined.