中华妇产科杂志
中華婦產科雜誌
중화부산과잡지
CHINESE JOUNAL OF OBSTETRICS AND GYNECOLOGY
2014年
12期
919-924
,共6页
杜静%王泽%张江涛%贾丽丽%张凤丽%石玉华%陈子江
杜靜%王澤%張江濤%賈麗麗%張鳳麗%石玉華%陳子江
두정%왕택%장강도%가려려%장봉려%석옥화%진자강
多囊卵巢综合征%受体,胰岛素%多态性,单核苷酸%疾病遗传易感性
多囊卵巢綜閤徵%受體,胰島素%多態性,單覈苷痠%疾病遺傳易感性
다낭란소종합정%수체,이도소%다태성,단핵감산%질병유전역감성
Polycystic ovary syndrome%Receptor,insulin%Polymorphism,single nucleotide%Genetic predisposition to disease
目的 研究胰岛素受体(INSR)基因rs2252673位点单核苷酸多态性(SNP)与多囊卵巢综合征(PCOS)发病易感性的相关性,进一步确证INSR基因在PCOS发病中的风险.方法 选择2007年7月-2013年4月在山东大学附属生殖医院就诊的224例汉族PCOS患者(PCOS组)和192例因输卵管原因或男方原因的不孕患者(对照组);根据体质指数(BMI)对PCOS患者进行再分组,分为肥胖组(BMI≥25 kg/m2) 88例、非肥胖组(BMI＜25 kg/m2) 136例.同时以PCOS患者为先证者,采用由其父亲、母亲以及患者本人组成的224个满足经典传递不平衡检验(TDT)分析的核心家系为观察对象.提取基因组DNA,采用PCR技术和直接测序法分析INSR基因rs2252673位点SNP基因型,比较PCOS组与对照组患者、肥胖组与非肥胖组PCOS患者间基因型与等位基因频率的差异;并比较不同基因型的PCOS患者间临床、生化指标的差异,临床、生化指标包括年龄、BMI、睾酮、雌二醇、LH、FSH、空腹血糖(FBG)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL).采用Hardy-Weinberg平衡检验分析INSR基因rs2252673位点是否符合Hardy-Weinberg平衡定律,TDT分析法验证INSR基因rs2252673位点在PCOS核心家系中是否存在危险等位基因的过度传递.结果 PCR产物的测序结果显示,rs2252673位点存在CC、CG和GG 3种基因型.(1)PCOS组CC、CG和GG基因型频率分别为8.0％、38.8％和53.1％,对照组CC、CG和GG基因型频率分别为14.6％、42.2％和43.2％;PCOS组C、G等位基因频率分别为27.5％、72.5％,对照组分别为35.7％、64.3％.PCOS组与对照组患者间基因型和等位基因频率分别比较,差异均有统计学意义(P＜0.05).(2)不同基因型(包括CC、CG和GG基因型)的PCOS患者间各临床、生化指标比较,差异均无统计学意义(P＞0.05).将基因型CG和GG患者合并后,CG+GG基因型的PCOS患者的TC水平明显高于CC基因型患者(t=2.072,P=0.048),HDL水平明显低于CC基因型患者(t=2.274,P=0.026);CG+GG基因型患者的FBG、FINS水平也有升高的趋势,但分别与CC基因型患者比较,差异均无统计学意义(P＞0.05).(3)肥胖组GG、CG和CC基因型频率分别为52.3％、39.8％和8.0％,非肥胖组分别为53.7％、38.2％和8.1％;肥胖组G和C等位基因频率分别为72.2％和27.8％,非肥胖组分别为72.8％和27.2％.肥胖组与非肥胖组PCOS患者间基因型、等位基因频率分别比较,差异均无统计学意义(x2=0.054,P=0.974; x2=0.022,P=0.883).(4) Hardy-Weinberg平衡检验显示,INSR基因rs2252673位点基因型分布符合Hardy-Weinberg平衡定律(P＞0.05);TDT分析显示,INSR基因rs2252673位点存在传递不平衡,且危险等位基因G在患病子代中存在过度传递现象,差异有统计学意义(传递基因∶未传递基因=120∶88;x2=4.923,P=0.027).结论 INSR基因rs2252673位点SNP与PCOS的发病易感性相关,且这种相关性不受BMI的影响.携带INSR基因rs2252673位点G等位基因的女性可能有较高的PCOS发病风险.
目的 研究胰島素受體(INSR)基因rs2252673位點單覈苷痠多態性(SNP)與多囊卵巢綜閤徵(PCOS)髮病易感性的相關性,進一步確證INSR基因在PCOS髮病中的風險.方法 選擇2007年7月-2013年4月在山東大學附屬生殖醫院就診的224例漢族PCOS患者(PCOS組)和192例因輸卵管原因或男方原因的不孕患者(對照組);根據體質指數(BMI)對PCOS患者進行再分組,分為肥胖組(BMI≥25 kg/m2) 88例、非肥胖組(BMI＜25 kg/m2) 136例.同時以PCOS患者為先證者,採用由其父親、母親以及患者本人組成的224箇滿足經典傳遞不平衡檢驗(TDT)分析的覈心傢繫為觀察對象.提取基因組DNA,採用PCR技術和直接測序法分析INSR基因rs2252673位點SNP基因型,比較PCOS組與對照組患者、肥胖組與非肥胖組PCOS患者間基因型與等位基因頻率的差異;併比較不同基因型的PCOS患者間臨床、生化指標的差異,臨床、生化指標包括年齡、BMI、睪酮、雌二醇、LH、FSH、空腹血糖(FBG)、空腹胰島素(FINS)、總膽固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL).採用Hardy-Weinberg平衡檢驗分析INSR基因rs2252673位點是否符閤Hardy-Weinberg平衡定律,TDT分析法驗證INSR基因rs2252673位點在PCOS覈心傢繫中是否存在危險等位基因的過度傳遞.結果 PCR產物的測序結果顯示,rs2252673位點存在CC、CG和GG 3種基因型.(1)PCOS組CC、CG和GG基因型頻率分彆為8.0％、38.8％和53.1％,對照組CC、CG和GG基因型頻率分彆為14.6％、42.2％和43.2％;PCOS組C、G等位基因頻率分彆為27.5％、72.5％,對照組分彆為35.7％、64.3％.PCOS組與對照組患者間基因型和等位基因頻率分彆比較,差異均有統計學意義(P＜0.05).(2)不同基因型(包括CC、CG和GG基因型)的PCOS患者間各臨床、生化指標比較,差異均無統計學意義(P＞0.05).將基因型CG和GG患者閤併後,CG+GG基因型的PCOS患者的TC水平明顯高于CC基因型患者(t=2.072,P=0.048),HDL水平明顯低于CC基因型患者(t=2.274,P=0.026);CG+GG基因型患者的FBG、FINS水平也有升高的趨勢,但分彆與CC基因型患者比較,差異均無統計學意義(P＞0.05).(3)肥胖組GG、CG和CC基因型頻率分彆為52.3％、39.8％和8.0％,非肥胖組分彆為53.7％、38.2％和8.1％;肥胖組G和C等位基因頻率分彆為72.2％和27.8％,非肥胖組分彆為72.8％和27.2％.肥胖組與非肥胖組PCOS患者間基因型、等位基因頻率分彆比較,差異均無統計學意義(x2=0.054,P=0.974; x2=0.022,P=0.883).(4) Hardy-Weinberg平衡檢驗顯示,INSR基因rs2252673位點基因型分佈符閤Hardy-Weinberg平衡定律(P＞0.05);TDT分析顯示,INSR基因rs2252673位點存在傳遞不平衡,且危險等位基因G在患病子代中存在過度傳遞現象,差異有統計學意義(傳遞基因∶未傳遞基因=120∶88;x2=4.923,P=0.027).結論 INSR基因rs2252673位點SNP與PCOS的髮病易感性相關,且這種相關性不受BMI的影響.攜帶INSR基因rs2252673位點G等位基因的女性可能有較高的PCOS髮病風險.
목적 연구이도소수체(INSR)기인rs2252673위점단핵감산다태성(SNP)여다낭란소종합정(PCOS)발병역감성적상관성,진일보학증INSR기인재PCOS발병중적풍험.방법 선택2007년7월-2013년4월재산동대학부속생식의원취진적224례한족PCOS환자(PCOS조)화192례인수란관원인혹남방원인적불잉환자(대조조);근거체질지수(BMI)대PCOS환자진행재분조,분위비반조(BMI≥25 kg/m2) 88례、비비반조(BMI＜25 kg/m2) 136례.동시이PCOS환자위선증자,채용유기부친、모친이급환자본인조성적224개만족경전전체불평형검험(TDT)분석적핵심가계위관찰대상.제취기인조DNA,채용PCR기술화직접측서법분석INSR기인rs2252673위점SNP기인형,비교PCOS조여대조조환자、비반조여비비반조PCOS환자간기인형여등위기인빈솔적차이;병비교불동기인형적PCOS환자간림상、생화지표적차이,림상、생화지표포괄년령、BMI、고동、자이순、LH、FSH、공복혈당(FBG)、공복이도소(FINS)、총담고순(TC)、감유삼지(TG)、고밀도지단백(HDL)、저밀도지단백(LDL).채용Hardy-Weinberg평형검험분석INSR기인rs2252673위점시부부합Hardy-Weinberg평형정률,TDT분석법험증INSR기인rs2252673위점재PCOS핵심가계중시부존재위험등위기인적과도전체.결과 PCR산물적측서결과현시,rs2252673위점존재CC、CG화GG 3충기인형.(1)PCOS조CC、CG화GG기인형빈솔분별위8.0％、38.8％화53.1％,대조조CC、CG화GG기인형빈솔분별위14.6％、42.2％화43.2％;PCOS조C、G등위기인빈솔분별위27.5％、72.5％,대조조분별위35.7％、64.3％.PCOS조여대조조환자간기인형화등위기인빈솔분별비교,차이균유통계학의의(P＜0.05).(2)불동기인형(포괄CC、CG화GG기인형)적PCOS환자간각림상、생화지표비교,차이균무통계학의의(P＞0.05).장기인형CG화GG환자합병후,CG+GG기인형적PCOS환자적TC수평명현고우CC기인형환자(t=2.072,P=0.048),HDL수평명현저우CC기인형환자(t=2.274,P=0.026);CG+GG기인형환자적FBG、FINS수평야유승고적추세,단분별여CC기인형환자비교,차이균무통계학의의(P＞0.05).(3)비반조GG、CG화CC기인형빈솔분별위52.3％、39.8％화8.0％,비비반조분별위53.7％、38.2％화8.1％;비반조G화C등위기인빈솔분별위72.2％화27.8％,비비반조분별위72.8％화27.2％.비반조여비비반조PCOS환자간기인형、등위기인빈솔분별비교,차이균무통계학의의(x2=0.054,P=0.974; x2=0.022,P=0.883).(4) Hardy-Weinberg평형검험현시,INSR기인rs2252673위점기인형분포부합Hardy-Weinberg평형정률(P＞0.05);TDT분석현시,INSR기인rs2252673위점존재전체불평형,차위험등위기인G재환병자대중존재과도전체현상,차이유통계학의의(전체기인∶미전체기인=120∶88;x2=4.923,P=0.027).결론 INSR기인rs2252673위점SNP여PCOS적발병역감성상관,차저충상관성불수BMI적영향.휴대INSR기인rs2252673위점G등위기인적녀성가능유교고적PCOS발병풍험.
Objective This study is designed to determine whether an association exists between single nucleotide polymorphism (SNP) variant rs2252673 of insulin receptor(INSR) gene and polycystic ovarian syndrome (PCOS) in Han Chinese in order to identify INSR as a genetic susceptibility factor for PCOS.Methods A total of 224 women with PCOS,192 controls and 672 participants consisting of 224 trios (mother,father and offspring with PCOS) were recruited from the Hospital for Reproductive Medicine Affiliated to Shandong University,from July 2007 to April 2013.Genomic DNA was extracted according to the manufacturer' s protocol.SNP rs2252673 of INSR gene was amplified by PCR and then sequenced on an automated sequencer.Moreover,clinical and metabolic features of the patients with PCOS were compared according to the genotypes.The subjects were divided into twot groups according to body mass index (BMI),and then the results were compared between two groups.And the transmitted disequilibrium test (TDT) was applied for data analysis.Results (1) There were three kinds of genotype of CC,CG and GG.Genotype frequencies of rs2252673 were 8.0％,38.8％,53.1％ and 14.6％,42.2％,43.2％ in the PCOS group and the control group,respectively.The allele frequencies of C and G were 27.5％,72.5％ and 35.7％,64.3％ in the PCOS group and the control group,respectively.There were statistical differences in genotype frequencies and allele frequencies between two groups (all P＜0.05).(2)No significant differences were observed in the different genotype according to clinical and metabolic characteristics of women with PCOS (P＞0.05).But when merging the genotype CG and GG,carriers of the CG and GG genotypes in women with PCOS were slightly associated with total cholesterol (TC) levels (t=2.072,P=0.048) and lower high-density lipoprotein (HDL) levels (t=2.274,P=0.026).Although statistical significance was not achieved,there was an increased tendency in fasting blood glucose (FBG) and fasting insulin (FINS) levels in CG and GG genotypes in PCOS cases.(3)Between the obesity and the non-obesity with PCOS,there was no statistical significance in the genotype and allele frequencies (x2=0.054,P=0.974; x2=0.022,P=0.883).(4)The results of families based analysis shown that genotype distribution of the SNP rs2252673 was in Hardy-Weinberg equilibrium (P＞0.05).After the TDT,the G allele in SNP rs2252673 was over transmitted in families (transmitted∶ non-transmitted=120∶ 88; x2=4.923,P=0.027).There was a transmitted disequilibrium in rs2252673,which implies the association of INSR and PCOS were independent of population stratification.Conclusions There were a association between the SNP variant rs2252673 of INSR gene and the susceptibility to PCOS in Han Chinese women,which was independently of body mass index.The carrier of G allele frequency of rs2252673 may have higher risk of PCOS.
