Sex-specific association of the glucocorticoid receptor gene with extreme BMD.
To study the role of the GR gene on BMD regulation in the Chinese, a sex-specific association study was performed. The results indicated that GR variation contributed to the extreme BMD variation in the Chinese.


BACKGROUND
The glucocorticoid (GC) receptor (GR) gene is an important candidate gene for BMD regulation in GC-induced osteoporosis (GIO). However, no study has explored the genetic effects of the GR gene on BMD variation in the Chinese population.


METHODS
Our sample consisted of 800 unrelated subjects (400 women and 400 men) with extreme age-adjusted hip BMD Z-scores selected from a population composed of 1988 normal adult Chinese Han. Four single nucleotide polymorphisms (SNPs) in the GR gene were genotyped. Both single SNP and haplotype association analyses were conducted.


RESULTS
SNP rs1866388 (p(c) = 0.028) was found to be significantly associated with extreme BMD only in men. In both sexes, haplotypes involving rs1866388 and rs2918419 were found to have different frequency distributions in extremely low and high BMD groups (p(p) = 0.024, 0.001, and 0.002 in women and 0.002, 0.003, and 0.003 in men for window sizes of two, three, and four SNPs, respectively). Most shared haplotypes showed opposite effects between women and men.


CONCLUSIONS
For the first time, our study suggested the possible role of the GR gene on BMD regulation and sex specificity in the association of GR with extreme BMD in the Chinese.
Peng
Yu-Mei
YM
The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Lei
Shu-Feng
SF
Guo
Yan
Y
Xiong
Dong-Hai
DH
Yan
Han
H
Wang
Liang
L
Guo
Yan-Fang
YF
Deng
Hong-Wen
HW
D000328:Adult; D015519:Bone Density / Q000235:genetics*; D002681:China; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012727:Sex Characteristics; D017678:Sex Distribution
D011965:Receptors, Glucocorticoid