雄激素受体基因CAG多态性与迟发性性腺功能减退症的相关性研究

目的:研究雄激素受体基因(AR)重复序列(CAG)n多态性与迟发性性腺功能减退症(LOH)的关系,探讨LOH的发病机制。方法:共调查1 000例40～70岁中老年男性,其中19例迟发性性腺功能减退症患者,随机抽取127例正常健康中老年男性,测定甘油三酯(TG)、空腹血糖(FBG)、血清总睾酮(TT)、游离睾酮(fT),测量身高、体重、腰围(WC)、血压,并采用DNA测序方法进行AR基因外显子1氨基端转录调节区(CAG)n重复序列长度测定,比较两组各指标之间的差异。结果:(CAG)n重复次数为15～32(23.05±2.95)。正常健康中老年男性的体重指数(BMI)、FBG较LOH患者显著下降(P<0.01),而TG、TT及fT较LOH患者显著升高(P<0.01)。正常健康中老年男性AR基因(CAG)n重复数为22.54±3.06;LOH患者AR基因(CAG)n重复数为23.23±2.24;LOH患者(CAG)n重复数略高于正常健康人群,但两者比较无统计学意义(P=0.946)。(CAG)n重复长度显示:长组(n≥22)AR基因(CAG)n在LOH组和正常健康中老年男性组的频率分别为73.68%和48.82%(P<0.05)。相关分析显示:TT、fT与(CAG)n重复序列无明显相关性(r=0.04和r=0.025,P>0.05)。结论:LOH男性AR基因(CAG)n重复序列呈现多态性,长(CAG)n重复多态可能是LOH发病的遗传因素,但仍需进一步扩大样本量证实。

Polymorphism of AR gene CAG copy number and late-onset hypogonadism in males

Objective: To analyze the association of the androgen receptor(AR) gene CAG-STR with late-onset hypogonadism(LOH),and explore the pathogenesis of LOH.Methods: Our investigation involved 1 000 men aged 40-70 years.We randomly selected 127 normal old and middle-aged males and 19 cases of LOH.We detected their levels of Triglyceride(TG),fasting blood glucose(FBG),serum total testosterone(tT) and free testosterone(fT),measured their body mass index(BMI),height,waist circumference(WC) and blood pressure,and examined the length of CAG repeats of the AR gene in the peripheral blood by PCR.Results: The numbers of CAG repeats ranged from 15 to 32,with a mean value 23.05±2.95.The mean BMI and FBG were significantly lower(P<0.01),but TG,tT and fT remarkably higher in the normal than in the LOH men(P<0.01),while the mean length of(CAG)n repeat polymorphism showed no statistically significant difference between the two groups(22.54±3.06 vs 23.23±2.24,P =0.946).The frequencies of long alleles(n≥22) were significantly higher in the LOH than in the normal men(73.68% vs 48.82%,P <0.05).The numbers of CAG repeats had no significant correlation with tT(r=0.04,P>0.05) and fT(r=0.025,P>0.05).Conclusion: The AR gene CAG length showed polymorphism in LOH men.The long alleles(CAG)n(n≥22) repeat polymorphism in the AR gene may be a genetic factor for LOH,but it has to be confirmed by further investigation.