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[谷胱甘肽S-转移酶P1基因多态性标记与不育男性氧化应激参数的关联]

[Association of polymorphic markers of GSTP1 gene with oxidative stress parameters in infertility men].

作者信息

Kurashova N A, Dashiev B G, Bairova T A, Labygina A V, Kolesnikova L I

机构信息

Scientific Centre for Family Health and Human Reproduction Problems, Irkutsk, Russian Federation.

出版信息

Urologiia. 2020 Sep(4):84-89.

Abstract

UNLABELLED

Genetic factors cause various forms of male infertility in 30-50% of cases. The role of oxidative stress in male infertility has been broadly recognised, and the search for a new marker to determine the redox environment in semen has gained considerable interest.

AIM

to establish the association of two polymorphic loci Ile105Val, Ala114Val of the GSTP1 gene (glutathione transferase class pi-1) with the parameters of oxidative stress in men with infertility.

MATERIALS AND METHODS

the main study group consisted of 160 men of reproductive age with infertility (mean age - 29,9+/-5,3 years). The control group included 104 practically healthy men with realized reproductive function (average age - 30,2+/-3,6 years). Molecular and genetic study of polymorphisms of the GSTP1 gene was performed by using real-time PCR. The material for the study was DNA samples, the extraction of which was carried out from samples of whole venous blood. The components of lipid peroxidation and antioxidant protection were determined in the blood and ejaculate using spectrophotofluorometric METHOD: s. Resalts: While analyzing the frequency of occurrence of the Ile105Val polymorphism of the GSTP1 gene in men with infertility and fertile men, statistically significant differences were found at (2=7,487; p=0,024). No significant differences were found between the groups (2=3,823; p=0,14), when were compared the frequency distribution of the genotypes of the Ala114Val polymorphism of the GSTP1 gene in men diagnosed with infertility and fertile patients. In men with infertility, carriers of the GSTP1(Ile105Val) heterozygous polymorphism, associations of the studied gene were established with an increase in GSH activity by 7% and a decrease in GR by 20% in blood and a decrease in SOD activity by 8% in the ejaculate, in contrast, fertile men, carriers of heterozygous polymorphism GSTP1(Ile105Val), which have associations with an increase in total AOA blood by 20% and with a decrease in GPO activity by 24% in the ejaculate. In men with infertility, carriers of the heterozygous polymorphism of GSTP1(Ala114Val), associations of the studied gene were established with a decrease in -tocopherol concentration by 15%, an increase in GPO activity by 25% in blood and a decrease in SOD activity by 7% in ejaculate, in contrast, fertile men, carriers of heterozygous polymorphism GSTP1(l114Val), which have associations with an increase in the concentration of DK in blood by 19% and with a decrease in GST activity by 32% in the ejaculate.

CONCLUSION

identification of carriers of polymorphic loci Ile105Val, Ala114Val GSTP1, as well as determination of enzymes of the thiol disulfide system can be recommended for additional assessment of the risk of reproductive disorders in men.

摘要

未标注

在30%-50%的病例中,遗传因素导致各种形式的男性不育。氧化应激在男性不育中的作用已得到广泛认可,寻找一种新的标志物来确定精液中的氧化还原环境引起了相当大的兴趣。

目的

确定谷胱甘肽S-转移酶pi-1(GSTP1)基因的两个多态位点Ile105Val、Ala114Val与不育男性氧化应激参数之间的关联。

材料与方法

主要研究组由160名生殖年龄的不育男性组成(平均年龄-29.9±5.3岁)。对照组包括104名生殖功能正常的健康男性(平均年龄-30.2±3.6岁)。采用实时荧光定量PCR对GSTP1基因多态性进行分子遗传学研究。研究材料为DNA样本,从全静脉血样本中提取。采用分光光度荧光法测定血液和精液中的脂质过氧化成分和抗氧化保护成分。结果:分析不育男性和生育男性中GSTP1基因Ile105Val多态性的发生频率时,发现有统计学意义的差异(χ²=7.487;p=0.024)。比较不育男性和生育男性中GSTP1基因Ala114Val多态性基因型的频率分布时,两组之间未发现显著差异(χ²=3.823;p=0.14)。在不育男性中,GSTP1(Ile105Val)杂合多态性携带者,研究基因与血液中谷胱甘肽(GSH)活性增加7%、谷胱甘肽还原酶(GR)降低20%以及精液中超氧化物歧化酶(SOD)活性降低8%有关;相比之下,生育男性中GSTP1(Ile105Val)杂合多态性携带者,与血液中总抗氧化能力(AOA)增加20%以及精液中谷胱甘肽过氧化物酶(GPO)活性降低24%有关。在不育男性中,GSTP1(Ala114Val)杂合多态性携带者,研究基因与血液中生育酚浓度降低15%、GPO活性增加25%以及精液中SOD活性降低7%有关;相比之下,生育男性中GSTP1(Ala114Val)杂合多态性携带者,与血液中脱氢表雄酮(DHEA)浓度增加19%以及精液中谷胱甘肽S-转移酶(GST)活性降低32%有关。

结论

对于男性生殖障碍风险的额外评估,建议鉴定GSTP1基因多态位点Ile105Val、Ala114Val的携带者以及测定硫醇二硫化物系统的酶。

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