Association of a G2014A transition in exon 8 of the estrogen receptor-alpha gene with postmenopausal osteoporosis.
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.
Ongphiphadhanakul
B
B
Department of Medicine and Research Center, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. rabpk@mahidol.ac.th
Chanprasertyothin
S
S
Payattikul
P
P
Saetung
S
S
Piaseu
N
N
Chailurkit
L
L
Rajatanavin
R
R
D000368:Aged; D015519:Bone Density / Q000235:genetics; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha; D005091:Exons; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics*
D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004958:Estradiol