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The Association of MTHFR C677T and MS A2756G Polymorphisms and Hcy Level with Male Infertility

Author: LiuLing
Tutor: QianWeiPing
School: Shantou University
Course: Obstetrics and Gynecology
Keywords: Methylenetetrahydrofolate reductase (NADPH2) Polymorphism, genetic 5-methyltetrahydrofolate-homocysteine S-methyltransferase Cysteine Infertility,male
CLC: R698.2
Type: Master's thesis
Year: 2011
Downloads: 102
Quote: 0
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Abstract


The cause of male infertility was complicated. Abnormality in sperm quality and quantity might account for 25% of human infertility and 85% of male infertility. Nowadays, human sperm quality might be effected by many factors, such as chromosomal abnormality, Y chromosome microdeletion, varicocele, cryptorchidism, epididymis damage, obstructive azoospermia and urogenital infection. However, spermatogenetic malfunction, which was caused by chromosomal abnormality and gene mutation, occupied 30% of male infertility. Besides, the idiopathic infertility, which was also called unexplained infertility, still took a certain percentage of 31.6. Therefore, it was particularly important to explore the pathogenesis of male infertility and provide effective treatment for male infertility.Methylenetetrahydrofolate reductase(MTHFR), methionine synthase(MS) and homocysteine(Hcy) were the main components of the folic acid metabolic pathway. Currently, there were some debates on the association of the gene polymorphism-C677T in the MTHFR gene and male infertility while few reports on the association of MS A2756G with male infertility. The polymorphisms of MTHFR C677T and MS A2756G were reported to be associated with the level of the human plasma Hcy, the increase of which might lead to impaired spermatogenesis or be related to the occurrence of oligospermia and/or asthenospermia directly or indirectly. The aim of this study was to investigate the association of MTHFR C677T, MS A2756G polymorphisms and the level of Hcy with male infertility, and to explore the pathogenesis of male infertility, so that we could find out the susceptible genes or risk factors, which might provide a theoretical basis to guide clinical practice for the prevention and treatment of male infertility.The experimental group included 75 cases of infertile male with oligospermia, asthenospermia or teratospermia. 72 control cases of fertile male with normal fertile history and sperm quality were taken as control group in this study. The technique of Polymerase chain reaction-Restriction fragment length polymorphism(PCR-RFLP) was used to detect the genetic polymorphisms of MTHFR C677T and MS A2756G, fluorescence quantitative test kit of Hcy was also used to detect the plasma homocysteine level. Results were as follows: 1. The frequency distribution of MTHFR C677T genotypes(CT, TT and CT+TT) in experimental group were higher than control group(P<0.05), and the frequency of T allele in the experimental group was also higher (P<0.05).2. The frequency of T allele in teratospermia group was higher than control group(P<0.05), which implied that T allele was associated with teratospermia .3. The frequency distribution of MS A2756G polymorphism genotypes and alleles between the control and experimental groups were not significantly different (p>0.05).4. The Hcy level was significantly higher in experimental group(p<0.05). In all subjects, the Hcy level in the MTHFR genotypes(CT, TT and CT+TT) was higher than that in CC genotype(p<0.05, p<0.01, p<0.01), but no significantly difference among the three MS A2756G genotypes(p>0.05).5. In control group, the Hcy level in CTAA genotype was significantly higher than that in CCAA genotype(P<0.01). The Hcy level in TTAA genotype was higher than that in CCAA genotype in experiment group(P<0.05). In all subjects, the Hcy level in TTAA genotypes was higher than that in CCAA genotypes(P<0.01). It was demonstrated that MTHFR C677T polymorphisms was associated with maleinfertility, in which CT and TT genotypes were the susceptibility genes for male infertility. T allele might be a risk factor for male infertility,as well as its association with teratospermia. However, there was no association between the MS A2756G polymorphism and male infertility. The change of MTHFR C677T polymorphism might result in male infertility through increasing the level of Hcy, which might be one of the pathogenesis of male infertility. There might be some synergistic actions between CT or TT genotype of MTHFR C677T with AA genotype of MS A2756G, resulting in increased level of the Hcy.

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CLC: > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Men 's sexual dysfunction > Male infertility
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