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黄体生成素与抗氧化物通路基因多态性与男性不育相关性研究

发布时间:2018-07-31 13:44
【摘要】:目的:不孕不育已成为一个全球性的问题,正受到越来越多的关注。在引起不孕不育的因素中,男女双方各占50%。男性不育是一个复杂、多因素疾病,其中遗传因素是重要病因之一。下丘脑-垂体-性腺轴中的黄体生成素以及抗氧化物通路中的酶[超氧化物歧化酶2(SOD2)、对氧磷酯酶1(PON1)、醌氧化物还原酶1(NQO1)]对精子的生成都起着不可替代的作用。黄体生成素与抗氧化物酶基因的多态性会影响黄体生成素以及抗氧化物酶的活性,影响其功能的正常发挥,进而造成生精障碍。虽然国内外对黄体生成素基因多态性以及抗氧化物通路中酶基因多态性与男性不育之间的相关性进行了研究,但是由于样本量大小及种群选取范围不同,导致研究结果也各不相同。为了更加清楚的认识黄体生成素基因多态性以及抗氧化物通路基因多态性与男性不育之间的关系。本研究分析了LHB(rs34349826和rs6521),SOD2 rs4880,PON1 rs662以及NQO1 rs1800566与男性不育发病风险的相关性。方法:利用病例-对照组的方法共收集829例样本,包括405例不育男性(非梗阻性无精子症145例、严重少精子症173例以及轻度少精子症87例)作为病例组,424例已正常生育的男性作为对照组,利用Mass ARRAY i PLEX GOLD分型检测技术对LHB rs34349826、LHB rs6521、SOD2 rs4880、PON1 rs662以及NQO1rs1800566共4个基因5个位点进行分型,并利用SPSS20.0对分型结果进行logistic回归分析。结果:通过病例组与对照组比较,在年龄、雌二醇以及睾酮这3项水平上无统计学差异,黄体生成素、卵泡刺激素存在有显著的差异(P0.05)。logistic回归分析结果显示LHB rs34349826以及LHB rs6521与男性不育之间无明显相关性,而在单倍型分析中,A-G(LHB rs34349826-rs6521)单倍型可以降低少精子症组男性不育的发病风险(P=0.004,OR=0.33,95%CI=0.15-0.72)。G-G单倍型基因对男性不育来说是一个保护因素(总病例组中:P=0.000,OR=0.52,95%CI=0.42-0.65,非梗阻性无精子症组中:P=0.001,OR=0.54,95%CI=0.40-0.75,严重少精子症组中:P=0.013,OR=0.70,95%CI=0.53-0.93,轻度少精子症组中:P=0.000,OR=0.22,95%CI=0.13-0.37)。SOD2 rs4880、PON1 rs662、NQO1 rs1800566与男性不育之间无明显相关性,并且基因-基因交互作用与男性不育之间也没有相关性。结论:LHB rs34349826、rs6521与男性不育之间不存在相关性,但单倍型分析发现,G-G单倍型可降低男性不育的发病风险,对男性不育来说是一个保护因素。SOD2 rs4880、PON1 rs662、NQO1 rs1800566与男性不育之间无明显相关性,并且基因-基因交互作用与男性不育之间也无明显相关性。
[Abstract]:Objective: infertility has become a global problem and is receiving more and more attention. Among the factors causing infertility, 50 are male and female. Male infertility is a complex, multivariate disease, in which genetic factors are one of the important causes. Luteinizing hormone in hypothalamus-pituitary-gonad axis and enzymes in antioxidant pathway [superoxide dismutase 2 (SOD2), p-oxaphosphatase 1 (PON1), quinone oxide reductase 1 (NQO1)] play an irreplaceable role in spermatogenesis. The polymorphism of luteinizing hormone and antioxidant enzyme gene will affect the activity of luteinizing hormone and antioxidant enzyme, affect the function of luteinizing hormone and antioxidant enzyme, and cause spermatogenesis obstacle. Although the relationship between luteinizing hormone gene polymorphism and enzyme gene polymorphism in antioxidant pathway and male infertility has been studied at home and abroad, the sample size and population selection range are different. The results also varied. In order to understand the relationship between luteinizing hormone gene polymorphism, antioxidant pathway gene polymorphism and male infertility. The relationship between LHB (rs34349826 and rs6521) SOD2 rs4880 PON1 rs662 and NQO1 rs1800566 and the risk of male infertility was analyzed. Methods: a total of 829 samples were collected from a case-control group, including 405 infertile men (145 non-obstructive azoospermia). 173 cases of severe oligozoospermia and 87 cases of mild oligozoospermia) were used as control group. Four loci of LHB rs349826 LHB rs652rs4880 PON1 rs662 and NQO1rs1800566 were classified by Mass ARRAY i PLEX GOLD. The results of typing were analyzed by logistic regression with SPSS20.0. Results: there was no significant difference in age, estradiol and testosterone between the case group and the control group. There was significant difference in follicle stimulating hormone (P0.05). Logistic regression analysis showed that there was no significant correlation between LHB rs34349826 and LHB rs6521 and male infertility. In haplotype analysis, haplotype A G (LHB rs34349826-rs6521) can reduce the risk of male infertility in oligozoospermia group (P0. 004). G-G haplotype gene is a protective factor for male infertility. G-G haplotype gene is a protective factor for male infertility. In the heavy oligozoospermia group, there was no significant correlation between the rs1800566 of P0: P0. 013, ORT 0.70rs662NQO1 and male infertility, while in the mild oligozoospermia group, there was no significant correlation between the percentage of 0. 2295) and the male sterility, and there was no significant correlation between the ratio of P0. 0. 013 and 0. 37) .SOD2 rs4880 and PON1 rs662NQO1 rs1800566. And there is no correlation between gene-gene interaction and male infertility. Conclusion there is no correlation between male sterility and male sterility, but haplotype analysis shows that G-G haplotype can reduce the risk of male infertility, and it is a protective factor for male infertility. There is no significant correlation between G-G haplotype and male infertility. There was no significant correlation between gene-gene interaction and male infertility.
【学位授予单位】:江苏大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R698.2

【参考文献】

相关期刊论文 前2条

1 龚道元;李子萍;庄锡伟;张晓林;康梅;廖异平;;男性不育患者精浆对氧磷酶-1活性测定的临床价值[J];南方医科大学学报;2012年09期

2 商学军,黄宇烽,徐建平,王咏梅;超氧化物歧化酶在男性不育症检测中的意义[J];男科学报;1998年03期



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