绝经后妇女雌激素受体β基因多态性与血管性痴呆的相关性研究

Correlational study on polymorphism of estrogen receptor β gene and vascular dementia

目的:探讨绝经后女性雌激素受体β基因(Estrogen receptorβ,ESR2)CA重复序列多态性及G1082A多态性与血管性痴呆(VD)的关系。方法:随机抽取盐城地区绝经后女性40例作为对照组,40例VD绝经期女性患者为试验组。采用基因扫描及DNA测序技术分析ESR2基因CA重复序列多态性,采用多聚酶链反应-限制性片段长度多态性法分析ESR2基因G1082A多态性;VD采用简易精神状态检查(MMSE-R))和临床痴呆分级表的判定。结果:以CA重复序列平均数22次为界,将重复序列基因分为短基因(<22)和长基因(≥22),分别以S和L表示。40例绝经后女性中CA重复序列基因型SS、SL及LL的频率分别为0.252、0.464和0.729;G1082A基因型rr、Rr及RR的频率分别为0.430、0.420和0.150;基因型频率分布均符合Hardy-Weinberg平衡(P>0.05)。在校正高血压、糖尿病、嗜烟酒、肥胖等混杂因素后,SS、SL基因型在VD患者中均较对照组高,差异均存在统计学意义,其中以SS基因型最为显著(P<0.001),SL基因型显著性稍逊(P<0.05),LL基因型与对照组相比差异无统计学意义(P>0.05),SL和LL基因型与DD型相比较,SL和LL基因型与SS型差异均存在统计学意义(P<0.01)。这2个ESR2基因的多态性位点非连锁不平衡(P>0.05)。结论:绝经女性中,ESR2基因第5内含子的CA重复序列多态性可能对VD的遗传调节起作用,而ESR2基因第5外显子的G1082A多态性可能对VD无明显影响。

Objective：To explore the relationship between CA repeat sequence polymorphism and G1082A polymorphism of estrogen receptor β gene and vascular dementia in postmenopausal women.Methods：40 healthy postmenopausal women（control group） and 40 postmenopausal women with vascular dementia（experimental group） in Yancheng were selected.CA repeat sequence polymorphism of estrogen receptor β gene was analysed by gene scan and DNA genetic sequencing technique,G1082A polymorphism of estrogen receptor β gene was analysed by polymerase chain reaction-restriction fragment length polymorphism.Vascular dementia was determined by simple and easy mental status examination（MMSE-R） and Clinical Dementia Rating（CDR）.Results：CA repeat sequence genes were divided into short genes and long genes according to average repeat times（22 times）,designated as S and L,respectively.The frequencies of genotypes in 40 postmenopausal women were as follows：SS（0.252）,SL（0.464）,LL（0.7292） for CA repeat polymorphism and rr（0.430）,Rr（0.420）,RR（0.150） for G1082A polymorphism.The distribution of genotypes was in Hardy-Weinberg equilibrium.After adjusting for hypertension,urophthisis,addicted to tobacco and alcohol and obesity,the frequencies of SS genotype and SL genotype in experimental group were higher than those in control group,especially SS genotype（P〈0.001）,but there was no difference in frequency of LL genotype between experimental group and control group（P〉0.05）,compared with DD genotype,there was difference between SL genotype,LL genotype and SS genotype（P〈0.01）.In different genotypes for GI082A polymorphism,there was no significant difference in VD.The estrogen receptor β gene polymorphism was not in linkage disequilibrium（P〉0.05）.Conclusion：In postmenopausal women,CA repeat polymorphism in the fifth intron of estrogen receptor β gene contributes to the genetic regulation of vascular dementia,but the G1082A polymorphism in the fifth exon of estrogen receptor β gene doesn＇t affect vascular dementia.