Browsing by Author "D.V.S. Sudhakar"

Now showing 1 - 2 of 2

Novel mutations in calcium/calmodulin-dependent protein kinase IV (CAMK4) gene in infertile men
(2012) A. Khattri; V.P. Reddy; R.K. Pandey; D.V.S. Sudhakar; N.J. Gupta; B.N. Chakravarty; M. Deenadayal; L. Singh; K. Thangaraj
Calcium/calmodulin-dependent protein kinase IV (CAMK4) is a multifunctional serine/threonine protein kinase, which plays an important role in the spermatogenesis by phosphorylating protamines. It has been shown to be involved in the regulation of human sperm motility. Moreover, the Camk4 knockout mice were infertile because of severely reduced sperm count and morphological abnormalities. As no study is available on the association of this gene with male infertility, we analysed all the exons of CAMK4 gene in ethnically matched 283 infertile and 268 fertile Indian men. We identified twenty nucleotide substitutions, of which twelve were novel. Of these novel variants, eight were exclusively detected in infertile men. Moreover, two infertile men-specific mutations were non-synonymous replacing amino acids at the highly conserved region. In silico analysis predicted both of these mutations as 'deleterious'. In addition to nucleotide substitutions, we identified five novel insertion-deletion mutations; of these, g.150264_66delGCG was exclusively found in two oligoasthenoteratozoospermic men. In silico analysis of infertile men exclusive mutations predicted that they can alter/diminish the potential binding sites of splicing factors, which may affect the mRNA splicing and protein translation. Our study suggests that the mutations in CAMK4 may lead to abnormal semen parameters. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.
SNPs in ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway and risk of male infertility in the Asian populations: association study, meta-analysis, and trial sequential analysis
(Springer New York LLC, 2019) Vertika Singh; Sandeep Kumar Bansal; D.V.S. Sudhakar; Neelabh; Arijit Chakraborty; Sameer Trivedi; Gopal Gupta; Kumarasamy Thangaraj; Singh Rajender; Kiran Singh
Purpose: We investigated if substitutions in the ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway correlate with non-obstructive azoospermia and male infertility. Methods: A total of 548 azoospermic infertile males and 410 fertile controls were genotyped for XRCC1 399A > G, 280G > A, and ERCC1 C > A 3′ UTR and 541 azoospermic infertile males and 416 fertile controls were genotyped for ERCC2 751A > C using iPLEX Gold Assay. Meta-analyses were performed on XRCC1 399A > G (1022 cases and 1004 controls), ERCC1 C > A 3′ UTR (879 cases and 1059 controls), and ERCC2 751A > C (914 cases and 850 controls) polymorphisms to quantitatively estimate the significance of the association between these polymorphisms and the risk of infertility. Results: Statistically significant association between ERCC2 751A > C SNP and male infertility was found using the codominant model (p = 0.03). Results of meta-analysis suggested a lack of correlation with male infertility risk, which could be due to pooling of studies from different ethnic populations. Due to limited the number of studies, a stratified analysis for different ethnic groups could not be performed. Conclusion (s): In conclusion, AA genotype of 751A > C SNP in ERCC2 correlated with a higher risk of male infertility and may contribute to an increased risk of azoospermia and male infertility in Indian men. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.