Singh K, Singh S K, Raman R
Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India.
J Postgrad Med. 2010 Oct-Dec;56(4):267-9. doi: 10.4103/0022-3859.70935.
DNA methylation is an important epigenetic feature of DNA that plays a pivotal role in gene expression regulation during spermatogenesis. The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyses the formation of folate intermediates that are vital for DNA synthesis and methylation reactions. C677T and A1298C variants of MTHFR result in reduced plasma folate and increase the susceptibility to various multifactorial disorders. We have already shown that homozygosity for 677 (C ®T) mutation in the MTHFR gene, is a risk factor for idiopathic male infertility in an Indian population.
Recently, we showed that homozygosity for the 677(C;T) mutation in the MTHFR gene is a risk factor for idiopathic male infertility and now we aim to assess whether the A1298C mutation in the same gene is an additional risk factor for idiopathic male infertility in an Indian population.
In a case-control study 151 idiopathic male infertile patients and 140 healthy fertile control individuals were recruited from the University hospital and infertility clinics in Varanasi city, India.
Genotyping for A1298C change of the MTHFR gene was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical Analysis : Allele frequencies were calculated using Fisher's exact test. Odds ratio was calculated as the measure of the association between the MTHFR genotype and idiopathic male infertility.
The homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in idiopathic azoospermic infertile men (OR=3.4494, CI: 1.0092 to 11.7899, P<0.05).
The MTHFR 1298CC genotype is an additional genetic risk factor for idiopathic male infertility in an Indian population.
DNA甲基化是DNA重要的表观遗传特征，在精子发生过程中的基因表达调控中起关键作用。亚甲基四氢叶酸还原酶（MTHFR）催化叶酸中间体的形成，这些中间体对DNA合成和甲基化反应至关重要。MTHFR的C677T和A1298C变异会导致血浆叶酸水平降低，并增加患各种多因素疾病的易感性。我们已经表明，MTHFR基因677（C→T）突变的纯合性是印度人群特发性男性不育的一个危险因素。
最近，我们发现MTHFR基因677（C；T）突变的纯合性是特发性男性不育的一个危险因素，现在我们旨在评估同一基因中的A1298C突变是否是印度人群特发性男性不育的另一个危险因素。
在一项病例对照研究中，从印度瓦拉纳西市的大学医院和不孕不育诊所招募了151例特发性男性不育患者和140名健康有生育能力的对照个体。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对MTHFR基因的A1298C变化进行基因分型。统计分析：使用Fisher精确检验计算等位基因频率。计算比值比作为MTHFR基因型与特发性男性不育之间关联的度量。
MTHFR基因的纯合（C/C）A1298C多态性在特发性无精子症不育男性中具有统计学高度显著性（OR=3.4494，CI：1.0092至11.7899，P<0.05）。
MTHFR 1298CC基因型是印度人群特发性男性不育的另一个遗传危险因素。
