Codon 325 sequence polymorphism of the estrogen receptor alpha gene and bone mineral density in postmenopausal women

Estrogen receptor alpha (ER alpha) encoding gene is one of the candidate ge nes to be involved in the development of osteoporosis. Until now correlatio n between three ER gene polymorphisms (identified with PvuII, XbaI and BstU I) and bone mineral density (BMD) have been investigated. The results of th ese studies are contradictory. Thus the aim of our work was to search for n ew, yet unknown, and probably more informative polymorphism(s) of the ER al pha gene. For detection of mutations the whole coding region of the ER alph a gene was screened systematically. In a group of 85 late postmenopausal wo men all of the eight exons were amplified by polymerase chain reaction (PCR ) and fragments were further analyzed by single-stranded conformation polym orphism (SSCP) analysis. Mutations were confirmed by direct DNA sequencing. In the whole coding region of the ER alpha gene two silent mutations in co don 87 and 325, respectively, were found. The silent mutation in codon 85 o f exon I (GCG --> GCC; A87A) was described previously, as BstUI polymorphis m. On the other side, the silent mutation in codon 325 (CCC --> CCG; P325P) , located in exon 4, has not been analyzed so far in correlation with BMD. According to the distribution of genotypes CC:CG:GG = 49.4:41.2:9.4, we can affirm the existence of genetic polymorphism in codon 325 in our populatio n of late postmenopausal women. The mean femoral neck BMD, but not the lumb ar spine BMD, was significantly lower (P = 0.029) in the homozygous GG-wome n with CCG/CCG codon 325 as compared to the homozygous CC-women with the no rmal codon CCC/CCC. Our results suggest that codon 325 sequence polymorphis m of the ER alpha gene might be one of the factors associated with low femo ral neck BMD. (C) 2001 Elsevier Science Ltd. All rights reserved.