Association of estrogen receptor β and estrogen-related receptor α gene polymorphisms with bone mineral density in postmenopausal women

Abstract

The aim of the study was to investigate the possible association of AluI and RsaI polymorphisms of estrogen receptor β (ER-β) gene and 23-bp nucleotide repeat polymorphism of estrogen-related receptor α (ERRα) gene with bone mineral density (BMD) in postmenopausal Egyptian women. Two-hundred postmenopausal osteoporotic women as cases and 180 healthy age-matched postmenopausal women as controls were genotyped by PCR fragment length polymorphism for AluI, allele-specific PCR for RsaI, and by sizing of PCR products on agarose gels for ERRα repeats. sRANKL levels were estimated by ELISA. BMD measurements for spine and femoral neck were performed by dual energy X-ray absorptiometry. A significant difference between women with osteoporosis and controls regarding allele and genotype distributions of AluI G/A (OR 2.37, 95 % CI 1.77-3.18 and p < 0.001 for A allele) and ERRα polymorphisms (for the two repeats allele OR 2.08, 95 % CI 1.09-4.00, and p = 0.02). Osteoporotic women with the AluI AA + GA genotype or with the EERα 2,2 genotype had significantly lower BMD than did women with the other genotypes. Moreover, there was a significant increase of the mean values of sRANKL in carriers of AluI A, RsaI A alleles and in patients having 2,2 genotypes of ERRα (p < 0.001, p < 0.001, p = 0.02, respectively). We demonstrated an association of ER-β AluI G/A and ERRα 23-repeats polymorphisms with BMD in postmenopausal Egyptian women. A possible effect of ER-β and ERRα polymorphisms on the levels of sRANKL was estimated.

Associations between ERα/β gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: a systematic review and meta-analysis

“…ERβ Rsa I is another important polymorphism of ERβ. Our subgroup analysis revealed a significant association between ERβ Rsa I and PMOP risk in overall populations, which is consistent with the studies of Shoukry et al [ 30 ], and Huang et al [ 31 ].…”

“…1 . Fourteen studies [ 11 – 24 ] reported the association between ERα Xba I and PMOP risk, and the number of the included studies that reported the alleles and genotypes of ERα Pvu II, ERα G2014A, ERβ Alu I and ERβ Rsa I was 16 [ 11 – 25 , 32 ], 4 [ 26 – 29 ], 4 [ 17 , 30 – 32 ] and 2 [ 30 , 31 ], respectively. Ivanova et al [ 20 ], Albagha et al [ 33 ], Aerssens et al [ 24 ], Kurt et al [ 34 ], Ge et al [ 36 ] and Pérez et al [ 19 ] reported both the lumbar spine and femoral neck BMD (g/cm 2 ).…”

“…ERβ has been found to be more abundant than ERα in trabecular bone, and more potent than ERα in mediating estrogen-induced repression of TNF-α expression, which is considered an important contributor to PMOP [ 30 ]. ERβ Alu I is one of the widely-studied ERβ gene polymorphisms, knowing that it could alter mRNA stability and protein levels, leading to reduced synthesis of ERβ [ 30 ]. In our study, ERβ Alu I was found to be significantly associated with increased risk of PMOP in Asian populations, while no significant relationship was observed in overall and Caucasian populations.…”

Association between IGF-1 polymorphisms and risk of osteoporosis in Chinese population: a meta-analysis

“…Many genes with innumerous gene polymorphisms have been identified to be covert risk alleles for osteoporosis vulnerability. Up to now, a series of candidate genes like vitamin D receptor [ 7 , 8 ], estrogen receptors [ 9 , 10 ], osteoprotegerin [ 11 , 12 ], have been widely reported to be associated with osteoporosis.…”

Purinergic P2X7 receptor functional genetic polymorphisms are associated with the susceptibility to osteoporosis in Chinese postmenopausal women

“…In an attempt to identify the genes involved in the pathogenesis of OP, a number of candidate genes, such as the vitamin D receptor (VDR) [7], estrogen receptor (ER) [8,9], and collagen type Ia1 (COLIA1) [10,11] genes, have been examined in association and/or linkage studies; however, they were found to be variably associated with BMD and the risk of OP. Together, these genetic variants only account for a small part of the total genetic variance in osteoporosis; other candidate genes require examination of their contribution to explain the genetic basis of OP.…”