Investigation of MTHFR, NR5A1 gene polymorphisms in association with infertility in couples: A case-control and in silico study

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-01-08 DOI:10.1016/j.genrep.2025.102128

Mandeep Kaur , Rajinder Kaur , Harmanpreet Singh Kapoor , Kiran Chhabra , Preeti Khetarpal

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Abstract

Polymorphisms in the genes that encode folate related enzymes are potential risk factors for infertility. Several studies have suggested that genetic polymorphisms in MTHFR and NR5A1 genes may play a significant role in the pathophysiology of infertility. Still the results are contradictory and further, no study has been reported from Malwa region of Punjab. The present study aimed to investigate the association of genetic variants in the MTHFR (C677T, A1298C), NR5A1 (A66G) genes and the risk of infertility. A case-control study was conducted on 197 male subjects, with 92 cases and 105 controls; and 197 female subjects, with 96 cases and 101 controls. Genotyping was performed by polymerase chain reaction-restriction length polymorphism (PCR-RFLP) and confirmed by Sanger sequencing. Genotype-tissue expression was observed using GTEx portal. To evaluate the deleterious SNP prediction six in silico tools (I-Mutant 2.0, PolyPhen-2, SNPs & GO, SIFT, RegulomeDB and CADD) were used. A significant difference was observed between cases and controls for MTHFR A1298C among females. MTHFR A1298C gene variant was associated with increased risk of primary and secondary infertility among females. NR5A1 A66G gene variant is associated with decreased risk of primary infertility among males. MTHFR C677T, A1298C and NR5A1 A66G are found to decrease the stability of protein. Genetic variants in the MTHFR gene (A1298C) and NR5A1 (A66G) could be an important predisposing genetic factor to infertility. However, further studies are needed to confirm the findings in large sample size.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.