维生素D受体基因和雌激素受体基因多态性与老年人低骨量的关系

目的探讨维生素D受体基因(VDR)和雌激素受体基因(ESR1)多态性与老年男性、女性低骨量的关系。方法 378名老年男性平均年龄(61.1±7.0)岁,其中260名健康男性、110例骨量减少和8例骨质疏松患者]和334名绝经后妇女平均年龄(58.4±6.3)岁,其中148名健康女性、153例骨量减少和33例骨质疏松患者]共712人,均为居住在上海30年以上汉族人。用双能X线测量仪检测上述受试者左侧股骨颈骨密度(bone mineral density,BMD)。按照股骨颈BMD低于同性别正常峰值BMD的-1～-2.5和-2.5标准差为标准诊断骨量减少和骨质疏松,排除继发性低骨量。检测VDR基因FokⅠ、ApaⅠ、CDX 2位点ESR 1基因的PvuⅡ和XbaⅠ位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)。结果 378名老年男性中,FokⅠ的基因型频率为FF(28.0%)、Ff(50.0%)和ff(22.0%),ApaⅠ的基因型频率为AA(9.5%)、Aa(43.4%)和aa(47.1%);CDX 2的基因型频率为AA(22.2%)、AG(45.8%)和GG(32.0%);PvuⅡ的基因型频率为PP(14.1%)、Pp(46.0%)和pp(39.9%);XbaⅠ的基因型频率为XX(5.0%)、Xx(36.8%)和xx(58.2%)。334名老年女性中,FokⅠ的基因型频率为FF(25.7%)、Ff(55.1%)和ff(19.2%),ApaⅠ的基因型频率为AA(10.2%)、Aa(44.0%)和aa(45.8%);CDX 2的基因型频率为AA(22.8%)、AG(47.9%)和GG(29.3%);PvuⅡ的基因型频率为PP(9.9%)、Pp(45.2%)和pp(44.9%);XbaⅠ的基因型频率为XX(2.1%)、Xx(36.8%)和xx(61.1%)。等位基因频率分布均符合Hardy-Weinberg定律。老年男性和女性的骨质疏松组、骨量减少组和骨量正常组之间上述基因SNP频率分布未见差异(P均0.05)。结论 VDR的FokⅠ、ApaⅠ及CDX 2位点和ESR 1的PvuⅡ及XbaⅠ位点多态性可能不是纳入本研究汉族老年男性和女性低骨量的风险因子,尚需更大样本量的实验予以证实。

The study of VDR and ESR1 gene polymorphisms with low bone mass of old men and women

Objective Our study aims to explore the relationship among polymorphisms of VDR and ESR1 gene with low bone mass of old men and women. Methods 378 （ aged 61.6 ± 7.0 years） old men （260 healthy men, 110 osteopenia patients and 8 osteoporosis patients） and 334 （ aged 58.4 ± 6. 3 years） postmenopausal women （ 148 healthy women, 153 osteopenia patients and 33 osteoporosis patients） with a total of 720 subjects were recruited. All subjects belonged to the Chinese Han ethnic group and lived in Shanghai more than thirty years. Bone mineral density （BMD） of left femoral neck was measured by dual energy X-ray absorptiometry （ GE Lunar Prodigy）. The diagnosis of osteopenia and osteoporosis are 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. The VDR Apa I , Fok I , CDX2 genotype and ESR1 Pvu II, Xba I genotype were determined by polymerase chain reactionrestriction fragment length polymorphism （PCR- RFLP） in all the subjects. Results Among 378 old men, the frequencies distributions of Fok I genotypes were FF （28.0%）, Ff （50. 0% ）, ff （22.0%）, and of Apa I genotypes were AA （9. 5% ）, Aa （43.4%）, aa （47. 1% ） ; and ofCDX2 genotypes were AA （22.2%）, AG （45.8%）, GG （32.0%）; and of Pvu II genotypes were PP （14. 1% ）, Pp （46.0%）, pp （39. 9% ） ; and of Xba I genotypes were XX （5.0%）, Xx （36. 8% ）, xx （58. 2% ）. Among 334 old women, the frequencies distributions of Fok I genotypes were FF （25.7%）, Ff （55.1%）, ff （19. 2% ）, and of Apa I genotypes were AA （9. 5% ）, Aa （43.4%）, aa （47. 1% ） ; and of CDX2 genotypes were AA （22.8%）, AG （47.9%）, GG （29.3%）; and of Pvu II genotypes were PP （9.9%）, Pp （45.2%）, pp （44.9%）; and of Xba I genotypes were XX （2.1%）, Xx （36.8%）, xx （61.1%）. Both to the old men and women, all allele frequencies did not deviate from Hardy-Weinberg equilibrium. The frequencies of all these loci＇s genotypes didn＇t show difference among osteoporosis group, osteopenia group and the normal bone mass group. Conclusion Our study suggest that the polymorphisms in VDR and ESR1 might not be risk factors of low bone mass of old men and women of Chinese ethnic group.