Whole Exome Sequencing of a Family with Non-obstructive Azoospermia Men did not Show the C۶۷۷T Variant as an Infertility Risk Factor

It is widely shared that the genetic variants in the genes encoding enzymes involved in folatemetabolism are important risk factors for male infertility [۱]. Since the MTHFR enzyme has asignificant role in the human folate and homocysteine metabolism, the folic acid supplements havereported to increase total sperm count [۲]. The association between )chr۱.exon۵:c.C۶۶۷T:p.A۲۲۲V (variant in the coding region of the human MTHFR gene which leads to the replacement of the alaninenumber ۲۲۲ by valine (exon۵:c.C۶۶۷T:p.A۲۲۲V) is controversial. Some studies reported this variant aspathogenic with almost ۳۰% and ۷۰% less enzymatic activity in heterozygotes (CT) and mutanthomozygotes individuals (TT) respectively, whereas other studies did not [۳,۴]. So, this variation oughtto be the subject of more studies to determine its pathogenic association with male infertility. This studyaimed to investigate the presence of the A۲۲۲V variant in fertile and infertile individuals of an Iranianfamily. Whole exome sequencing (WES) in the family under study with three non-obstructiveazoospermia and two normal individuals referred to the Infertility and Reproductive BiomedicineResearch Center of Royan Institute, Tehran, Iran was performed. After bioinformatic analysis of theobtained data, the heterozygous C۶۷۷T variant in both affected and normal siblings was detected andthe variant was not co-segregated with phenotype in the family members. Our investigation showed thatthe MTHFR C۶۷۷T variant is not a risk factor for male infertility.

کلیدواژه ها:

WES ، MTHFR ، rs۱۸۰۱۱۳۳ ، non-obstructive azoospermia ، infertility