KITLG基因rs995030和rs4474514位点单核苷酸多态性与男性不育相关性研究

目的:探讨酪氨酸激酶受体的特异性配体(KITLG)基因rs995030和rs4474514位点单核苷酸多态性与男性不育之间的相关性。方法:收集南京周边地区特发性男性不育患者360例(病例组),已生育的健康男性338例(对照组);按照WHO《人类精液检查与处理实验室手册》第5版,将病例组分为无精子症组(n=143)、严重少精子症组(n=159)和少精子症组(n=58)。收集所有研究对象的临床基本资料,并采集病人外周血提取基因组DNA,用Sequence Mass-Array技术检测KITLG基因rs995030和rs4474514位点的基因型,通过Logistic回归分析两位点基因多态性与男性不育的相关性。结果:病例组与对照组比较,精子浓度[(13.23±24.52)×10~6/ml vs(78.74±61.25)×10~6/ml]、前向运动精子百分率[(18.71±15.19)%vs(39.36±9.75)%]、FSH[(16.09±17.31) IU/L vs(4.56±2.41) IU/L]差异显著(P0.01)。经Logistic回归分析,未发现各基因型与男性不育有统计学意义的相关性,亚组分析也未发现相关性。结论:KITLG基因rs995030和rs4474514位点的单核苷酸多态性与男性不育无显著相关性,后续可以通过扩大样本量以及样本选取范围来进一步研究验证。     

乙酰基转移酶2基因单核苷酸多态性与男性不育发病风险的相关性研究

目的:探讨乙酰基转移酶2基因(NAT2)的rs1799930和rs1799931单核苷酸多态性与南京地区男性不育发病风险的相关性。方法:采用病例-对照研究,选取636例特发性男性不育患者作为病例组,年龄20~44(28.45±4.38)岁;442例有生育史的健康男性作为对照组,年龄21~35(28.30±3.46)岁。取外周静脉血,用Sequenom Mass Array技术检测这2个位点的基因型,Logistic回归模型分析不同基因型与男性不育的相关性,单倍型分析2个位点连锁效应和4种基因型组合与男性不育的关系。结果:病例组和对照组精子浓度[(32.32±45.49)×10~6/ml vs(72.77±45.21)10~6/ml]、前向运动精子百分率[(15.29±5.06)%vs(42.02±9.04)%]、卵泡刺激素水平[(14.69±12.37)U/L vs(4.72±2.51)U/L]差异有统计学意义(P均0.01),其他参数病例组与对照组无统计学意义的差异。2个位点各基因型频率和等位基因频率在各种模型中均与男性不育无统计学意义的相关性;单倍型分析表明,rs1799930和rs1799931存在连锁效应(D'=0.998,r_2=0.05),但4种基因型组合与男性不育也无明显相关性。结论:NAT2基因的rs1799930和rs1799931位点的单核苷酸多态性与特发性男性不育的发病风险无相关性。该位点与男性不育具体关系有待更大样本量加以证实。     

TP53基因rs1042522单核苷酸多态性与男性不育相关性研究

目的:探讨肿瘤蛋白p53(TP53)基因rs1042522位点单核苷酸多态性与男性不育的关系。方法:采用病例-对照研究,收集南京地区特发性男性不育患者380例(病例组),有生育史的健康男性398例(对照组);并将病例组分为无精子症组(n=140)和少精子症组(n=240)。用Sequence Mass Array技术检测TP53基因rs1042522位点的基因型,通过Logistic回归分析该位点多态性与男性不育的相关性。结果:病例组与对照组前向运动精子百分率[(10.38±5.57)%vs(42.55±9.57)%]、精子浓度[(13.13±24.96)×106/ml vs(77.34±49.24)×106/ml]、T[(14.07±5.36)nmol/L vs(11.89±4.50)nmol/L]、FSH[(16.80±18.20)U/L vs(4.55±7.17)U/L]存在显著性差异(P0.05)。经Logistic回归分析,未发现各基因型与男性不育有统计学意义的相关性,亚组分析也未发现相关性。结论:TP53基因rs1042522位点的单核苷酸多态性与男性不育无显著相关性。     

精子Tektin-2基因单核苷酸多态性与特发性弱精子症的相关性研究

目的探讨Tektin-2基因的单核苷酸多态性(SNP)位点rs12043423与特发性弱精子症的相关性。方法采用病例对照法,随机选取特发性弱精子症患者192例作为弱精子症组,另募集同期208例精子活力正常的不育男性作为不育症组和213例精液正常的已生育男性作为正常对照组,所有研究对象均进行精液分析,对三组患者Tektin-2基因的SNP位点rs12043423进行基因分型,比较三组间的基因型和等位基因频率,并且进行与特发性弱精子症的关联分析。结果 (1)弱精子症组Tektin-2基因的SNP位点rs12043423的CC基因型频率显著低于正常对照组及不育症组,TT基因型频率则显著增加(P<0.05),而CT基因型频率在三组间的分布频率无显著性差异(P>0.05)。弱精子症组C等位基因的分布频率显著低于正常对照组和不育症组,而T等位基因的频率显著高于正常对照组和不育症组(P<0.05)。不育症组和正常对照组比较,不同基因型的分布频率及等位基因的频率在两组间均无显著性差异(P>0.05)。(2)弱精子症组与正常对照组比较,Tektin-2基因突变(杂合子[CT]和纯...     

MDM2基因启动子区rs2279744位点单核苷酸多态性与乳腺癌发病关系的Meta分析

目的:探讨鼠双微体基因(MDM2)启动子区rs2279744位点单核苷酸多态性与乳腺癌发病风险的关系。方法:检索多个国内外文献数据库,收集MDM2启动子区rs2279744位点基因多态性与乳腺癌的风险关系的病例对照研究,筛选出符合标准的文献,提取数据后行Meta分析,并对结果进行敏感性分析与发表偏倚评价。结果:共纳入28篇文献,共计乳腺癌病例组11 804例,对照组15 209例。Meta分析结果显示,总人群中突变型与野生型(TG/GG vs.TT)与等位基因(G vs.T)均有明显差异(OR=1.15,95%CI=1.06~1.24,P0.001;OR=1.12,95%=1.05~1.18,P0.001);按洲别分亚组分析显示,两者仅在亚洲人群中有明显差异(TG/GG vs.TT:随机效应模型OR=1.34,95%CI=1.15~1.57,P0.001,固定效应模型OR=1.34,95%CI=1.20~1.50,P0.001;G vs.T:随机效应模型OR=1.21,95%CI=1.09~1.35,P=0.001)。敏感性分析与Egger检验显示结论可靠,无明显偏倚。结论:亚洲人群MDM-2基因rs2279744位点的突变纯合子/杂合子(GG/TG)型相对于野生型(TT)的个体乳腺癌发病风险增加,MDM-2基因rs2279744位点的突变与亚洲人群乳腺癌密切相关。     

常染色体DAZL基因单核苷酸多态性与男性不育相关性研究

目的:探讨常染色体DAZL基因单核苷酸多态性(SNP)与男性不育的关系。方法:收集东北地区男性不育症患者(不育组,n=144)和健康并已育有一子女的男性(生育组,n=53)精液标本,不育组按照WHO(1999)少、弱和畸形精子分类标准分成少弱畸形精子症组(n=17)、少弱精子症组(n=33)、弱畸形精子症组(n=13)、弱精子症组(n=54)和非少弱畸形精子不育症组(n=27),应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)筛选SNP260多态性,应用聚合酶链反应-单链构象多态性分析(PCR-SSCP)筛选SNP386多态性,并测序验证和进行统计学分析。结果:不育组及生育组中均检测到SNP260A→G多态性,统计学分析差异无显著性(P>0.05),但在少弱畸形精子症组SNP260AG基因型比例大于其他各组;各研究组均未发现SNP386多态性。结论:SNP260和SNP386多态性与中国东北地区男性不育无相关性。前者AG基因型与少弱畸形精子的关系尚需进一步证实;后者多态性可能仅分布在台湾的一些狭小地区,两者均不能作为东北地区男性不育基因诊断的分子标志。     

ERCC2单核苷酸多态性对宁夏原发性男性不育的影响

目的:探讨DNA修复基因(ERCC2)单核苷酸多态性(SNPs)rs13181、rs1618536和SNPrs1799793对宁夏原发性男性不育的影响。方法:采用病例-对照研究方法,运用MassArray SNP技术,对宁夏地区351例原发性男性不育患者[年龄22~38(31.0±4.2)岁]和327例健康生育对照人群[年龄19~42(33.0±5.9)岁]的ERCC2 SNP rs13181、rs1618536和rs1799793进行分型检测。结果:ERCC2 SNP rs13181、rs1618536和rs1799793基因型频率和等位基因频率在病例组和对照组中的分布无统计学意义(P0.05),其中AnyG-anyA-anyA突变基因型频率在两组中分布具有统计学差异(OR=0.414,95%CI=0.176~0.970)。结论:ERCC2 SNP rs13181、rs1618536和rs1799793在宁夏地区男性原发性不育中存在交互作用,随着联合突变位点的增多,不育症的发病风险增加。     

FGFR2基因单核苷酸多态性与乳腺癌的相关性研究

目的：探讨成纤维细胞生长因子受体2（FGFR2）基因第二内含子单核苷酸多态性与女性乳腺癌发生的相关性。方法：运用等位基因扩增-聚合酶链反应（ASA-PCR）方法结合琼脂糖凝胶电泳技术,对200例女性乳腺癌患者（乳腺癌组）和200例正常女性（对照组）进行检测,分析两组人群FGFR2基因第二内含子的三个单核苷酸位点rs2912778r、s3135718和rs11200014的多态性分布,并进行统计学分析。结果：rs2912778（T/T、T/C、C/C）r、s3135718（A/A、A/G、G/G）r、s11200014（A/A、A/G、G/G）的基因型分布在对照组和乳腺癌组之间的差异有明显的统计学意义（P〈0.01）;根据病理分型进一步分析,三个位点野生型与变异型相比差异均无统计学意义（P〉0.05）。结论：FGFR2基因第二内含子的三个位点单核苷酸多态性可能与中国女性乳腺癌的发生有关。     

ABCA2基因单核苷酸多态性与胆囊结石病的相关性

目的 检测中国人ABCA2(ATP binding cassette A2)基因编码区单核苷酸多态性(single nucleotide polymorphism,SNP),并探讨其与中国汉族人群胆囊结石病的关系。方法 采用直接测序法检测ABCA2基因编码区及相邻的部分内含子的序列,以确定中国人ABCA2基因SNPs的位置及类型。对位于编码区的SNPs,采用病例对照方法,在胆囊结石病患者和正常对照者中进行关联研究。结果在16 911 bp测序长度中,共发现12个SNP,2个位于编码区,10个位于内含子,其中7个为新发现的SNP。各SNPs在胆石病组和对照组中分布差异无统计学意义。结论SNP在不同种族间存在差异。ABCA2基因编码区SNP在胆石病和对照组间分布差异无统计学意义。     

XPC基因多态性与男性不育的相关性研究

目的:位于XPC基因外显子区域Ala499Val(C>T)和Lys939Gln(A>C)两个非同义突变的单核苷酸多态性位点在人群中研究广泛,具有潜在的功能性,其多态的变化影响到XPC基因的结构和功能,进而影响到DNA损伤修复率。本文探讨了这两个位点基因多态性在中国汉族人群中的分布及其与男性不育发病风险的关联。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,分析318例男性不育患者和228例正常对照男性中XPC基因两个多态性位点的基因分型和等位基因频率,以及这两个位点单独和联合作用与男性不育的相关性。结果:在Ala499Val(C>T)多态性位点中,CC、CT、TT三种基因型频率在病例和对照组中的分布存在显著性差异(P=0.020)。携带TT基因型的个体罹患男性不育的风险是CC基因型个体的0.49倍(95%CI=0.23～0.88),是(CC+CT)基因型个体的0.39倍(95%CI=0.22～0.71)。Lys939Gln(A>C)多态性位点与男性不育的患病风险无显著性关联。联合两个位点分析,个体携带1～4个危险位点患男性不育的风险是携带零个的2.75倍(95%CI=1.50～5.04)。结论:XPC基因Ala499Val(C>T)基因多态性与男性不育的发病风险存在关联,可能是我国汉族人群男性不育的遗传易感因素之一。     

亚甲基四氢叶酸还原酶单核苷酸多态性与男性不育研究进展

许多不明原因的男性不育是由于参与精子发生过程中相关基因的突变而导致其生精过程异常。亚甲基四氢叶酸还原酶(MTHFR)参与DNA、RNA、蛋白质代谢过程,并与精子生成密切相关。已发现MTHFR基因有20种以上单核苷酸多态性。目前研究提示,MTHFRC677T、A1298C多态性与男性不育可能存在密切关系。本文对这两种多态性与男性不育的关系做一综述,并指出新发现的MTHFRG1793A多态性与男性不育的关系有待研究揭示。     

The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis

To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT?+?CT vs. CC: OR?=?4.14, 95%CI?=?2.48–6.89; CT vs. CC: OR?=?4.34, 95%CI?=?2.56–7.34; T vs. C: OR?=?4.35, 95%CI?=?2.58–7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.     

Human catalase gene polymorphism (CAT C‐262T) and risk of male infertility

Infertility is the failure of a couple to engender after endeavouring at least one full year of unprotected intercourse. It has been reported that reactive oxygen species contributed to pathogenesis of various disease. To inactivate ROS cells biosynthesise several antioxidant enzymes, one of them is catalase which contributes H₂O₂ to H₂O and O₂. This study set out to delineate the association of catalase C‐262T polymorphism with idiopathic male infertility. The study included 195 men with idiopathic infertility and 190 healthy volunteers. Genomic DNA was extracted from peripheral blood leucocytes. Genotype and allele frequencies were determined in patients and controls using allele‐specific PCR (AS‐PCR). The prevalence of genotype frequencies of the CAT CC/CT/TT was 31.79%, 65.12% and 3.07%, respectively, in infertile subjects, as against 24.73%, 55.26% and 20%, respectively, in healthy volunteers. Statistical analysis has emerged significant difference from the comparison of either genotype (P < 0.05). Taking into accounts of results, the catalase C‐262T polymorphism indicates that CAT‐262T/T genotype confers less susceptibility to male infertility. Further studies with larger numbers of patients are required for further evaluation and confirmation of our finding.     

酪氨酸蛋白激酶-2 rs2230724基因多态性与结直肠癌风险相关性研究

目的探讨酪氨酸蛋白激酶-2（JAK2）基因rs2230724多态性与结直肠癌风险的相关性。 方法采用多聚酶链式反应-限制性内切酶片段长度多态性（PCR-RFLP）方法分析110例结直肠癌患者（病例组）和150例非肿瘤患者（对照组）JAK2 rs2230724基因的多态性,并对该多态性与结直肠癌风险的相关性进行评估。采用SPSS 26.0软件进行分析。采用拟合优度χ²检验进行Hardy-Weinberg平衡的检测。两组间的一般资料、基因型和等位基因的频率分布的比较采用Student’s t检验和Pearson χ²检验。采用Logistic线性回归（需要进行校正）分析JAK2 rs2230724基因多态性和结直肠癌风险的相关性,相对危险度用优势比（OR）和95%可信区间（CI）估计。以P<0.05为有统计学意义。 结果病例组A等位基因频率明显高于对照组,A等位基因突变增加50%结直肠癌发病风险（P=0.025,OR=1.50,95%CI=1.05-2.14）。与野生基因型（GG）相比,变异基因型（AG+AA）增加79%结直肠癌发病风险（P=0.043,校正OR=1.79,95%CI=1.02-3.15）。其中,突变纯合子（AA）基因型的携带者结直肠癌的风险增加129%（P=0.034,OR=2.29,95%CI=1.06-4.93）,差异有统计学意义。但是,在添加了校正因素后,差异无统计学意义（P=0.052,校正OR=2.29,95%CI=0.99-5.26）。而且,在分层分析中,在高年龄组（年龄>56）、非吸烟受试者和城市居住者中,该多态性增加结直肠癌风险（P<0.05）。 结论在江苏汉族人群中JAK2基因rs2230724多态性与增加结直肠癌风险相关。     

Association of the methylenetetrahydrofolate reductase gene C677T polymorphism with the risk of male infertility: a meta-analysis

Several molecular epidemiological studies have been conducted to examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and male infertility susceptibility, but the results remain inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. In this meta-analysis, a total of 26 case–control studies including 5659 infertility cases and 5528 controls were selected to evaluate the possible association. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to assess the strength of association of C677T polymorphism with male infertility in the additive model, dominant model, recessive model and allele-frequency genetic model. In the overall analysis, the frequency of the 677T allele was significantly associated with male infertility susceptibility (OR?=?2.32, 95%CI?=?2.04–2.65 for TT vs. CC genotype; OR?=?1.09, 95%CI?=?1.00–1.19 for CT vs. CC genotype; OR?=?1.19, 95%CI?=?1.10–1.29 for CT/TT vs. CC genotype; OR?=?1.54, 95%CI?=?1.36–1.74 for TT vs. CC/TT genotype; OR?=?1.22, 95%CI?=?1.15–1.30 for T vs. C allele). A subgroup analysis of the subjects showed that significantly strong association between MTHFR C677T polymorphism and male infertility was present only in Asians, but not in Caucasians. Additionally, MTHFR C677T was associated with a significant increase in the risk of azoospermia in all genetic models. Meanwhile, no significantly increased risks of oligoasthenotertozoospermia (OAT) were found in most of the genetic models. In conclusion, this meta-analysis is in favor that the MTHFR C677T polymorphism is capable of causing male infertility susceptibility, especially in Asians and the subgroup of azoospermia.     

Methylenetetrahydrofolate reductase C677T polymorphism and the risk of male infertility: a meta-analysis

Several molecular epidemiological studies have been conducted to examine the association between MTHFR C677T polymorphism and male infertility susceptibility, but the results remain inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 10 case-control studies, including 2275 cases and 1958 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals were used to assess the strength of association in the additive model, dominant model and recessive model. In the overall analysis, no significant association between the polymorphism and risk of male infertility was observed. Stratified analysis showed that significantly strong association between MTHFR C677T polymorphism and male infertility were present only in Asians (OR = 1.79 for TT vs. CC genotype; OR = 1.42 for CT/TT vs. CC genotype; OR = 1.50 for TT vs. CC/CT genotype; OR = 1.36 for T vs. C allele), but not in Caucasians. Additionally, MTHFR 677T was associated with a significant increase in the risk of azoospermia in all genetic models. No significantly increased risks of oligoasthenoteratozoospermia were found in any of the genetic models. In conclusion, this meta-analysis supports that MTHFR C677T polymorphism is capable of causing male infertility susceptibility in Asians, but not in Caucasians.     

鱼精蛋白基因多态性与男性不育相关性研究进展

鱼精蛋白(PRM)是精子中含量最丰富的富含精氨酸核蛋白,在精子生成过程中发挥重要作用。在精子发生过程后期PRM取代组蛋白,促使精子中的核基质与核蛋白之间的结合更紧密,从而使核内染色质高度富集、浓缩,防止精子基因组因内部或外部因素而诱发突变。随着DNA测序技术的发展,研究PRM基因多态性与男性生育关系成为一大热点。许多研究表明,PRM1基因rs2301365位点是男性不育的危险因素,会使男性罹患不育的风险增加27%~66%;PRM1基因rs737008位点和PRM2基因rs1646022位点在亚洲人中是男性罹患不育的保护因素;PRM1/PRM2比值也与男性不育存在强相关性。本文综述了PRM基因多态性与男性不育的研究进展。     

CFTR gene mutations and male infertility

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are a relatively frequent cause of male infertility. Depending on their molecular consequences, CFTR mutations may either result in typical cystic fibrosis (CF), one of the most common autosomal recessive disorders, which is characterized by chronic lung disease, pancreatic exocrine insufficiency, an increase in the concentration of sweat electrolytes and male infertility, due to obstructive azoospermia, or in atypical (often monosymptomatic) forms of CF such as congenital absence of the vas deferens (bi- or unilateral), bilateral ejaculatory duct obstruction or bilateral obstructions within the epididymides. All males with idiopathic obstructive azoospermia bear an increased risk for CF offspring. Couples requesting microsurgical epididymal sperm aspiration and in vitro fertilization, e.g. intracytoplasmic sperm injection, should be offered genetic counselling and molecular genetic analysis of the CFTR gene, if male infertility due to obstructive azoospermia is the underlying cause.