CAJ | 학술논문

目的探讨胆固醇侧链裂解酶CYP11A1基因多态性与多囊卵巢综合征(PCOS)发病的相关性.方法收集2005年5月-2008年12月于安徽医科大学第一附属医院妇产科门诊就诊的PCOS患者290例为PCOS组,同期就诊的安徽籍非PCOS患者344例为对照组,从人类基因组单体型图谱(HapMap)11期汉族数据库中选择CYP11A1基因覆盖区域的r~2>10.8的7个标签单核苷酸多态性(tSNP)位点(rs12438594、rs4077582、rs9806234、rs16968477、rs4887139、rs1843090、rs11632698)和3个微卫星位点(D15S1547、D16S520、D15S1546);采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术分析两组患者的基因型和等位基因频率,并进行多个位点联合分析(即单体型分析).结果 7个tSNP和3个微卫星位点中,两组患者的ra4077582、D15S1547、D15S1546和rs11632698位点的基因型频率比较,差异均有统计学意义(P=0.010、0.044、0.018和0.026);两组患者的rs4077582、rs4887139、rs1843090、D15S1547和D16S520位点的等位基因频率分别比较,差异均有统计学意义(P=0.002、0.048、0.030、0.001和0.024).ACGCA13/6/9AG、ACGTA16/6/11AA、GCACG12/8/8AA、GTACA14/4/7GG、GTGCA13/6/7AG 5种常见的CYP11A1基因单体型中,PCOS组患者的GTACA14/4/7GG和ACGCA13/6/9AG单体型频率分别为7.8%(45/580)和25.3%(147/580),分别与对照组(11.9%和19.6%)比较,差异均有统计学意义(P<0.05).两组rs4077582位点不同基因型患者血浆雄激素水平比较,差异均无统计学意义(P>0.05).结论 CYP11A1基因多态性与PCOS有一定的相关性,但与PCOS患者高雄激素水平之间的相关性需通过对tSNP及微卫星覆盖区域的序列进行进一步分析确定.
목적 탐토담고순측련렬해매CYP11A1기인다태성여다낭란소종합정(PCOS)발병적상관성.방법 수집2005년5월-2008년12월우안휘의과대학제일부속의원부산과문진취진적PCOS환자290례위PCOS조,동기취진적안휘적비PCOS환자344례위대조조,종인류기인조단체형도보(HapMap)11기한족수거고중선택CYP11A1기인복개구역적r~2>10.8적7개표첨단핵감산다태성(tSNP)위점(rs12438594、rs4077582、rs9806234、rs16968477、rs4887139、rs1843090、rs11632698)화3개미위성위점(D15S1547、D16S520、D15S1546);채용취합매련식반응-한제성편단장도다태성(PCR-RFLP)기술분석량조환자적기인형화등위기인빈솔,병진행다개위점연합분석(즉단체형분석).결과 7개tSNP화3개미위성위점중,량조환자적ra4077582、D15S1547、D15S1546화rs11632698위점적기인형빈솔비교,차이균유통계학의의(P=0.010、0.044、0.018화0.026);량조환자적rs4077582、rs4887139、rs1843090、D15S1547화D16S520위점적등위기인빈솔분별비교,차이균유통계학의의(P=0.002、0.048、0.030、0.001화0.024).ACGCA13/6/9AG、ACGTA16/6/11AA、GCACG12/8/8AA、GTACA14/4/7GG、GTGCA13/6/7AG 5충상견적CYP11A1기인단체형중,PCOS조환자적GTACA14/4/7GG화ACGCA13/6/9AG단체형빈솔분별위7.8%(45/580)화25.3%(147/580),분별여대조조(11.9%화19.6%)비교,차이균유통계학의의(P<0.05).량조rs4077582위점불동기인형환자혈장웅격소수평비교,차이균무통계학의의(P>0.05).결론 CYP11A1기인다태성여PCOS유일정적상관성,단여PCOS환자고웅격소수평지간적상관성수통과대tSNP급미위성복개구역적서렬진행진일보분석학정.
Objective To investigate the association between polymorphism of cytochrome P450 subfamily Ⅺ A polypeptide 1 (CYP11A1) gene and polycystic ovarian syndrome (PCOS) in Chinese population. Methods From May 2005 to Dec.2008,290 PCOS cases treated in the First affiliated hospital of Anhui Medical University matched with 344 reproductive women as controls were enrolled in this study. Genotypes of 7 tagging single nucleotide polymorphisms(tSNP,rs12438594,rs4077582,rs9806234,rsl6968477,rs4887139,rs1843090,rsl 1632698)covering CYP11A1 gene (r~2≥0.8) and 3 microsatellite markers (D15S1547,D16S520,D15S1546) were chosed from the phase II database of Han population in HapMap data.Genotype and frequency of allele were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype of gene polymorphism were analyzed in 290 PCOS cases and 344 controls.Results Among 7 tSNPs and 3 microsatellite markers,the frequency of rs4077582,D15S1547,D15S1546 and rsl 1632698 between two groups reached statistical difference (P =0.010,0.044,0.018 and 0.026).The allele frequency of rs4O77582,rs4887139,rsl843090,D15S1547 and Dl 6S520 showed significant difference between two groups(P=0.002,0.048,0.030,0.001 and 0.024).Among 5 haplotype of CYP11A1(ACGCA13/6/9AG,ACGTA16/6/11AA,GCACG12/8/8AA,GTACA14/4/7GG,GTGCA13/6/7AG),the frequency of GTACA14/4/7GG and ACGCA13/6/9AG were 7.8% (45/580) and 25.3% (147/580) in PCOS group and 11.9% and 19.6% in control group,which showed statistical difference (P< 0.05 ).There was no significant difference in the level of serum androgen at difference genotype from rs4077582 between two groups (P>0.05).Conclusion The polymorphism of CYP11A1 gene was associated with PCOS,however,the relationship between gene sequence covered by tSNP/microsatellite markers and hyperandrogenism of PCOS should be further investigated.