细胞色素P450基因多态性对围绝经期妇女潮热易感性的影响

Effect of estrogen metabolic enzyme cytochrome P450 gene polymorphism on susceptibility of hot flashes in perimenopause women

目的研究性激素水平及雌激素代谢酶相关基因细胞至色素P450（cytochrome P450,CYP）多态性对围绝经期妇女潮热易感性的影响。方法选取2006年10月至2008年5月西安交通大学第一附属医院体检中心进行健康体检的328名围绝经期妇女进行病例对照研究,将其分为潮热组（n=156）和无潮热组（n=172）。采用放免法测定血清卵泡刺激素（follicle stimulating hormone,FSH）、黄体生成素（luteinizing hormone,LH）、雌二醇（estradiol,E2）和睾酮（testosterone,T）,酶免法测定性激素结合球蛋白（sex hormone binding globulin,SHBG）和硫酸脱氢表雄酮（dehydroepiandrosterone sulfate,DHEA-S）。应用聚合酶链反应-限制性片段长度多态性方法分析两组妇女CYP17 Msp A1Ⅰ、CYP19Rsa I、CYP1A1 Msp I和CYP1B1 Eco57I基因多态性。结果与无潮热组妇女比较,潮热组妇女血清FSH水平增高（P〈0.01）,而E2和SHBG水平降低（P〈0.05）。CYP1B1 Eco57I基因多态性在潮热组和无潮热组妇女中的分布差异有统计学意义（P〈0.05）;携带CYP1B1 Eco57I基因多态性的妇女潮热发生的风险为未携带妇女的1.25倍（OR=1.25,95%CI：1.03-1.82）;中重度潮热发生及潮热持续时间〉1年的风险分别为未携带妇女的1.28倍和1.35倍。结论血清E2水平降低可能是潮热发生的原因之一。CYP1B1 Eco57I基因多态性增加妇女潮热发生、潮热程度和持续时间的风险。

Objective To explore the pathogenesis of hot flashes, and study the correlation of polymorphism of estrogen metabolic enzyme eytochrome P450 （CYP） gene and hot flashes in the perimenopause women. Methods Totally 328 perimenopausal women were selected randomly for case-control study, including 156 women with hot flashes in the case study group and 172 women without hot flashes in the control group. Follicle stimulating hormone （ FSH ）, luteinizing hormone （ LH ）, estradiol （ E2 ） and testosterone （T） were detected by radioimmunoassay. Sex hormone binding globulin （SHBG） and dehydroepiandrosterone sulfate （DHEA-S） were detected by enzyme linked immunosorbent assay. The gene polymorphisms of CYP17 MspA1 I , CYP19 RsaI, CYP1A1MspI and CYP1B1 Eco57I were detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The level of FSH was statistically higher, but the levels of E2 and SHBG were statistically lower in the women with hot flashes compared to the women without hot flashes （ all P 〈 0. 05 ）. The CYP1B1 Eco57I genotype was statistically significant between the women with hot flashes and the women without hot flashes （P 〈 0. 05 ）.The women with CYP1BI Eco57I polymorphism were 1.25 folds in the hot flashes risk （ OR = 1.25, 95% CI= 1.03 -1.82） , 1.28 folds in the severity and 1.35 folds in the duration （persisted for a year or longer） eompared to the women without hot flashes. Conclusion Low E2 level may he one of the reasons for hot flashes. Women with CYP1B1 Eeo57I polymorphism are more likely to have hot flashes with high severity and long duration.