【摘要】： 目的探討白細胞介素1 (interleukin-1,IL-1)B基因啟動子區(qū)-511、-31位點單核苷酸多態(tài)性( single nucleotide polymorphisms,SNPs)和白細胞介素1RN第2內(nèi)含子基因可變數(shù)目串聯(lián)重復多態(tài)性(Variable number of tandem repeat,VNTR)與寧夏漢族反復自然流產(chǎn)(recurrent spontaneous abortion,RSA)的相關性。 方法選取2006年1月-2008年12月在寧夏醫(yī)科大學遺傳實驗室進行染色體檢查的反復自然流產(chǎn)者191例患者做為病例組,年齡19-42歲,平均年齡為27.63±4.45歲;選取2008年1月-2008年12月在銀川市婦幼保健院住院分娩的正常孕婦193例做為對照組,年齡20-36歲,平均年齡為27.26±2.31歲。用聚合酶鏈反應-限制性片段長度多態(tài)性(polymerase chain reaction- restricted fragment length polymorphism,PCR-RFLP)技術檢測病例組與對照組各基因型,對IL-1B啟動子區(qū)域-511C/T、-31C/T SNP位點及IL-1RN內(nèi)含子2 VNTR基因進行PCR擴增,其中IL-1B(-511C/T)基因用AvaI限制性內(nèi)切酶對PCR產(chǎn)物進行消化,IL-1B(-31C/T)基因用AluI限制性內(nèi)切酶對PCR產(chǎn)物進行消化,2.0%瓊脂糖凝膠電泳分別對IL-1B、IL-1RN基因多態(tài)性進行分析。利用spss11.5軟件計算基因型頻率,等位基因頻率及比值比(OR),比較各組基因型頻率和基因頻率及相對危險度。 結(jié)果1、經(jīng)遺傳平衡定律檢驗,研究對象IL-1B、IL-1RN各基因型頻率分布均符合Hardy-Weinberg平衡法則,表明各基因頻率在寧夏人群中達到遺傳平衡,具有群體代表性。健康對照人群中,IL-1B啟動子區(qū)-511基因型CC、CT、TT頻率分別為24.9%、54.4%和20.7%;IL-1B啟動子區(qū)-31基因型CC、CT、TT頻率分別為18.6%、59.1%和22.3%;IL-1RN內(nèi)含子2(VNTR)等位基因檢測到A1、A2、A3、A4四種,基因型A1/A1、A1/A2、A1/A3、A1/A4和A2/A2分別為83.9%、11.9%、1.1%、2.0%和1.1%;反復自然流產(chǎn)患者中,IL-1B-511基因型CC、CT、TT頻率分別占27.8%、53.4%和18.8%,IL-1B啟動子區(qū)-31基因型CC、CT、TT頻率分別占14.7%、55.0%和30.3%;IL-1RN等位基因檢測到A1、A2、和A4三種,基因型A1/A1、A1/A2、A1/A4和A2/A2分別占75.4%、20.4%、1.1%和3.1%;IL-1B-511、-31位點基因型及等位基因患者組與健康對照組比較無顯著性差異(P0.05);IL-1RN基因型及等位基因頻率在患者和對照人群中分布有統(tǒng)計學意義(P0.05),攜帶有IL-1RN intron2 VNTR A1/A2基因型的個體發(fā)生反復自然流產(chǎn)的危險性比攜A1/A1基因型個體高,OR值分別為1.908(95%CI: 1.087～3.346);攜帶有IL-1RN intron2 VNTR等位基因A2 OR值為2.027(95%CI: 1.242～3.308)。 結(jié)論IL-1B-511、-31位點各基因型頻率和等位基因頻率在病例組與對照組中的分布無顯著性差異,提示攜帶有IL-1B-511和-31位點突變基因型的個體可能與反復自然流產(chǎn)的易感性無關。IL-1RN的等位基因IL-1RNA2的分布頻率及含等位基因IL-1RNA2的基因型在患者組均高于對照組,提示攜帶有IL-1RN的A2基因型尤其基因型為A1/A2的純合子,可能與反復自然流產(chǎn)的易感性有關。
[Abstract]:Objective to investigate the single nucleotides polymorphism (single nucleotide polymorphisms, at site 31 of IL-1 (interleukin-1,IL-1) B gene promoter region-511. the aim of this study was to investigate the single nucleotides polymorphism (single nucleotide polymorphisms, at site 31 of IL-1 B gene. The association between SNPs) and variable number tandem repeat polymorphism (Variable number of tandem repeat,VNTR) of IL 1RN intron 2 gene and recurrent spontaneous abortion (recurrent spontaneous abortion,RSA) in Ningxia Han nationality. Methods 191 patients with recurrent natural abortion who underwent chromosome examination in the Genetics Laboratory of Ningxia Medical University from January 2006 to December 2008 were selected as the case group with an average age of 27.63 鹵4.45 years. 193 normal pregnant women hospitalized in Yinchuan Maternal and Child Health Hospital from January 2008 to December 2008 were selected as the control group, with an average age of 27.26 鹵2.31 years. Polymerase chain reaction-restriction fragment length polymorphism (polymerase chain reaction- restricted fragment length polymorphism,PCR-RFLP) was used to detect the genotypes of the case group and the control group. The promoter region of IL-1B was-511C. -31C/T SNP site and IL-1RN intron 2 VNTR gene were amplified by PCR, in which IL-1B (- 511C/T) gene was digested by AvaI restriction endonuclease. IL-1B (- 31C/T) gene was digested by AluI restriction endonuclease and IL-1B,IL-1RN gene polymorphism was analyzed by 2.0% agarose gel electrophoresis. The genotypic frequency, allele frequency and ratio were calculated by spss11.5 software to compare the genotypic frequency, gene frequency and relative risk of each group. Results 1. Through the test of genetic equilibrium law, the frequency distribution of IL-1B,IL-1RN genotypic was in accordance with Hardy-Weinberg equilibrium law, which indicated that each gene frequency reached genetic balance in Ningxia population and was representative of population. In the healthy control population, the CC,CT,TT frequency of IL-1B promoter region-511 was 24.9%, 54.4% and 20.7%, respectively. The frequency of CC,CT,TT of IL-1B promoter region-31 was 18.6%, 59.1% and 22.3%, respectively. A1, A2, A3, A4, A1, A1 and A2/A2 were 83.9%, 11.9%, 1.1%, 2.0% and 1.1%, respectively, in IL-1RN intron 2 (VNTR), A1, A2, A4, A1, A1 and A1, respectively. In patients with recurrent spontaneous abortion, the CC,CT,TT frequency of IL-1B-511 genotype was 27.8%, 53.4% and 18.8%, respectively, and the CC,CT,TT frequency of IL 1B promoter region-31 genotype was 14.7%, respectively. 55.0% and 30.3%; Three kinds of A1, A2 and A4 were detected in IL-1RN, A1 鈮，

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