HOXD4基因多态性与老年男女性低骨量的关系

目的同源异形盒（homeobox，HOX）基因在调节软骨分化和成骨细胞中扮演了很重要的角色。本研究目的是探讨HOXD4基因多态性与老年男性和女性低骨量的关系。方法筛选711名（年龄61．8±6．9岁）老年男性（其中419例健康男性、276例骨量减少患者和16例骨质疏松患者）和617名（年龄58．9±6．4岁）绝经后妇女（其中272例健康女性、291例骨量减少患者和54例骨质疏松患者）共1328个研究对象，所有对象均为居住在上海30年以上的汉族人。双能X线吸收仪（GE Lunar Prodigy和Hologie QDR2000）检测左侧股骨颈BMD（bone mineral density，BMD）。骨量减少和骨质疏松的诊断分别按照股骨颈BMD为同性别正常峰值BMD的-1和-2．5个标准差，同时排除继发性低骨量的存在。使用Taqman荧光探针法检测HOXD4的3个标签位点：rs1867863、sr13418078和rs4972504的单核苷酸多态性（single nucleotide polymor-phisms，SNPs）。结果与其他人群不同，在我们的研究中rs13418078只发现CC基因型。在711例老年男性中，rs1867863的基因型频率依次为AA（40．5％）、AC（45．7％）、CC（13．8％），rs4972504的基因型频率依次为CC（51．6％）、CT（40．5％）、TT（7．9％）；在617例老年女性中，~1867863的基因型频率依次为AA（42．3％）、AC（43．1％）、CC（14．6％），rs4972504的基因型频率依次为CC（53．5％）、CT（38．7％）、TT（7．8％）；等位基因频率分布均符合Hardy—Weinberg定律。未发现此两位点SNP在骨质疏松组、骨量减少组和骨量正常组之间频率分布的差异（P均〉0．05）。结论本研究第一次提示了HOXD4的rs1867863和rs4972504位点多态性可能不是中国汉族老年男性和女性低骨量的风险因子。

The relationship of HOXD4 gene polymorphisms with low bone mass in old men and women

Objective Prior to bone formation, the HOX genes play a central role in the regulation of cartilage differentiation and in gene regulation on osteoblast. Our study aims to explore the relationship among polymorphism of HOXD4 gene with low bone mass of old men and women. Methods 711 （aged 61.8 ±6.9 years） old men （419 healthy men, 276 osteopenia patients and 16 osteoporotic patients） and 617 （aged 58. 9 ±6. 4 years） postmenopausal women （272 bea/thy women, 291 osteoperda patients and 54 osteoporotic patients） with a total of 1328 subjects were recruited. All the subjects belonged to the Chinese Hart ethnic group and lived in Shanghai more than 30 years. Bone mineral density （BMD） of left femoral neck was measured by dual energy X-ray absorptiometry （ GE Lunar Prodigy and Hologic QDR 2000）. The diagnosis of osteopenia and osteoporesis were according to cut-off value of femoral neck BMD of 1 to 2. 5 standard deviations below the average for peak BMD of the same sex and secondary low bone mass was excluded. Three tagging single nucleotide polymorphisms （SNPs） in HOXD4 were genotyped by Taqnum fluorescent probe methods： rs1867863, rs13418078 and rs4972504. Results Differed from other populations, in our study, rs13418078 was only found CC genotype. Among 711 old men, the frequencies distributions of rs1867863 genotype were AA （40. 5% ）, AC （45. 7% ） and CC （13. 8% ） and the frequencies distributions of rs4972504 genotype were CC （51.6%）, CT （40.5%） and TT （7. 9% ）. Among 617 old women, the frequeneies distributions of rs1867863 genotype were AA （42. 3% ）, AC （43. 1% ） and CC （ 14. 6% ） and the frequencies distributions of rs4972504 genotype were CC （53.5%）, CT （38. 7% ） and TT （7. 8% ）. Allele frequencies of rs1867863 and rs4972504 of old men and women all followed the Hardy-Weinberg equilibrium. The frequencies of rs1867863 and rs4972504 genotypes didn＇t show difference among osteoporesis group, osteopenia group and the normal bone mass