雄激素受体基因（CAG）n多态性与绝经后骨质疏松关系的研究

Study of relationship of an androgen receptor CAG repeat polymorphism with postmenopausai osteoporosis

目的探讨雄激素受体（AR）基因第1外显子三核苷酸胞嘧啶腺嘌呤-鸟嘌呤基因重复序列[（CAG）n]多态性在绝经后骨质疏松（PMO）发生中的作用。方法采用美国NORLAND公司的XR-46系列双能X线骨密度仪测量股骨颈及腰椎2～4（L2～4）骨密度，根据股骨颈和L2～4骨密度诊断为PMO分别为78例和108例（PMO组），非PMO分别为73例和60例（对照组）。采用基因扫描及DNA测序技术检测AR基因（CAG）n重复次数和基因型，探讨（CAG）n多态性与PMO的关系。结果检测到（CAG）n多态性的18、20、21、23、24、25、26、27、28、29及30次重复11个等位基因及16种基因型。基因型和等位基因频率分布在根据股骨颈骨密度诊断的PMO组（SS：25．6%，SL：39．7％，LL：34．6％；S：45．5%，L：54．5％）与对照组（SS：23．3％，SL：45．2％，LL：31．5％；S：45．9％，L：54．1％）比较，差异无统计学意义（均为P〉0．05）；SL基因型（OR=0．798，95％CI：0．335～1．797）、LL基因型（OR=0．998，95% CI：0．425～2．341）或SL＋LL基因型（OR=0．880，95％CI：0．419～1．852）者与SS型者比较，患PMO风险差异无统计学意义（均为P〉0．05）。L2～4骨密度诊断的PMO组的基因型和等位基因频率分布（SS：18．5％，SL：49．1％，LL：32．4％；S：43．1％，L：56．9％）与对照组（SS：21．7％，SL：45．0%，LL：33．3%；S：44．2％，L：55．8％）比较，差异无统计学意义（均为P〉0．05）；SL基因型（OR=1．276，95％CI：0．552～2．950）、LL基因型（OR=1．137，95％CI：0．468-2．766）或SL＋LL基因型（OR=1．217，95％CI：0．556～2．663）者与SS型者比较，患PMO风险差异亦无统计学意义（均为P〉0．05）。调整年龄、绝经时间、绝经年龄及体质指数后，Logistic回归分析显示，（CAG）n多态性与股骨颈及L2～4骨密度诊断的PMO均无相关性（P〉0．05）。结论AR基因（CAG）n多态性可能与PMO的发生无关。

Objective To study the relationship between a CAG repeat polymorphism of the androgen receptor （AR） gene and postmenopausal osteoporosis （PMO）. Methods Genotypes for the AR polymorphism were determined by gene scan and DNA sequence methods in a case-control study,including 78 cases of PMO at femoral neck and 73 cases as controls, and 108 cases of PMO at lumbar spine （L2-4） and 60 cases as controls . Bone mineral density for the proximal femur and L2-4 was measured by NORLAND XR 46 dual-energy X-ray absorptiometry. The relationship between the CAG repeat polymorphism and PMO was investigated. Results Eleven different allelic variants, containing 18, 20, 21, 23, 24, 25, 26, 27, 28, 29, and 30 CAG repeats were detected, 16 genotypes were present in the subjects. There were no significant differences in the genotype and allele distributions of （CAG）n polymorphism between PMO group （SS：25.6G ,SL;39.7% ,LL：34.6% ;S： 45.5% ,L：54.5%） and control group （SS：23.3% ,SL： 45.2%,LL：31.5%S;45.9% ,L：54.1%） at the femoral neck site （all P）0.05）. The risk of PMO at femoral neck in females with the genotypes of SL （OR：0. 798,95%CI：0. 335-1. 797）, the LL （OR：0. 998,95%CI：0. 425-2. 341）, and the combined SL and LL （OR： 0.880, 95% CI：0.419-1.852） were not significantly increased in comparison with those of females with the SS genotype （all P〉0.05）. There were no significant differences in the genotype and allele distributions of （CAG）n polymorphism between PMO group （SS： 18.5%, SL： 49. 1%, LL： 32.4% ; S： 43. 1%, L： 56.9%） and control group （SS： 21.7%, SL： 45.0%,LL：33.3%;S：44.2%,L：55.8%） at the L2 4 site （P〉0.05）. The risk of PMO at L2-4 in females with the genotypes of SL （OR：1. 276,95%CI：0. 552-2. 950）, the LL （OR：1. 137,95%CI： 0.468-2.766）, and the combined SL and LL （OR： 1.217, 95% CI： 0.556 - 2.663） were not significantly increased in comparison with those of females with the SS genotype （all P〉0.05）. After adjustments for age, postmenopausal period, menopausal age, and body mass index, the logistic regression analyses revealed the （CAG）n polymorphism was not significantly associated with PMO at the femoral neck and L2-4 site （all P〉0.05）. Conclusions The CAG repeat polymorphism in the AR gene may not be associated with PMO at the femoral neck and L2- 4 site.