Estrogen receptor α gene relationship with peak bone mass and body mass index in Chinese nuclear families

Abstract

Estrogen receptor alpha (ER-a) plays an important role in mediating estrogen signaling. Studies in Caucasian populations have shown that it is involved in endocrine-related diseases such as osteoporosis and obesity. In the present study, we first used a quantitative transmission disequilibrium test (QTDT) to examine the relationship between this gene and both the osteoporosis-related phenotype bone mineral density (BMD), and the obesity-related phenotype body mass index (BMI), in 384 Chinese nuclear families. We genotyped a dinucleotide repeat marker (TA) n , and a long-range haplotype was reconstructed using this marker and two other restriction fragment length polymorphism (RFLP) markers at PvuII and XbaI loci. Although we found significant total association [allele (TA) 21 with hip BMD (P=0.001), and haplotype Px(TA) 21 with spine (P=0.0007) and hip (P=0.0006) BMD], the more reliable within-family associations were not significant between these phenotype pairs. No linkage signal was obtained for either spine BMD or hip BMD. We found no association or linkage between any of the three studied polymorphisms and the long-range haplotypes of the ER-a gene and BMI. Our study does not support an association of the ER-a gene with BMD and BMI in the Chinese population.

Association analysis of genetic polymorphisms and potential interaction of the osteocalcin (BGP) and ER-α genes with body mass index (BMI) in premenopausal Chinese women

“…Recent studies of the association between the ER-α gene polymorphism and BMI have yielded conflicting results [20][21][22][23][24][25][26][27] . Our results are inconsistent with the previous findings in non-Chinese populations, indicating significant associations between the ER-α gene and BMI variation in postmenopausal Caucasian women [20] , middle-aged Japanese women [22] , postmenopausal white women [21] , African-American families [24] , Brazilian subjects [25] , and men from the Framingham Heart Study [23] .…”

“…ER and progesterone receptor status was used to define breast cancer risk factors [19] . Polymorphisms in the ER-α gene have been reported to be associated with BMI, though contradictory results were also reported [20][21][22][23][24][25][26][27] . Osteocalcin, also called bone Gla protein (BGP), is an osteoblast-specific protein that is known to play a role in bone growth and has recently been reported to function as a new metabolic hormone regulating the adiposity and glucose homeostasis in experimental animals [28][29][30] .…”

“…The polymorphism of the PvuII site in the ER-α gene is the most extensively studied genetic marker in relation to BMI variation. However, the results so far have been largely inconsistent and controversial [20][21][22][23][24][25][26][27] . In addition, no data have been provided about the associations between BGP polymorphisms and BMI variation.…”

Impact of ER gene polymorphisms on overweight and obesity in Down Syndrome

“…A recent study on Chinese families using a quantitative disequilibrium test failed to support associations of the ER α gene polymorphisms and BMI [24]. The interaction of various genetic and environmental factors could explain the different results in the Chinese study.…”

Association of estrogen receptor α gene PvuII and XbaI polymorphisms with non-small cell lung cancer

“…However, the association between polymorphisms of XbaI and PvuII in the ER-α gene and the risk of developing lung cancer remains unknown. With the exception of lung cancer, a number of other diseases including breast cancer (15,19,29), Alzheimer's disease (30), obesity (31,32), multiple sclerosis (33), endometriosis (34), uterine leiomyomas (35) and bone mineral density (32,36), have been evaluated for possible linkage with the two PvuII and XbaI polymorphism loci in the ER-α gene. Various ER-α genotypes may determine the differences in ER-α expression rather than impact on the final effects of ER-α (37).…”