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Novel Variants in UBE2B Gene and Idiopathic Male Infertility

KALIAPPAN GOPAL

NALINI J. GUPTA

BAIDYANATH CHAKRAVARTY

MAMTA DEENADAYAL

From the ^* Centre for Cellular and Molecular Biology, Hyderabad, India; the University of Madras, Chennai, India; the Institute of Reproductive Medicine, Salt Lake, Kolkata, India; and the Infertility Institute and Research Centre, Hyderabad, India.

Correspondence to: K. Thangaraj, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad-500 007, India (e-mail: thangs{at}ccmb.res.in).

The UBE2B gene encodes ubiquitin-conjugating enzyme, which is involved in DNA repair. Ube2b knockout mice were found to be infertile because of structural abnormality of sperm. However, there is no genetic study on the role of the UBE2B gene in human fertility; therefore, the present investigation was designed to study genetic variations in the UBE2B gene and its role in human male infertility. Sequence analyses of the UBE2B gene in 530 infertile (350 azoospermic, 105 oligoasthenoteratozoospermic, and 75 oligoasthenozoospermic) and 300 fertile control men revealed the presence of 5 substitution single-nucleotide polymorphisms (SNPs) in 221 individuals (199 infertile [37.5%] and 22 fertile [7.3%] men). Of these, 2 (g.5197:T>G; g.9157:A>G) of the 5 substitutions were novel and observed only in infertile men. Distribution of haplotypes TA, TG, GA, and GG are not uniform between the patient and the control group of this study. Interestingly, our study suggests that the haplotype TG conferred significantly increased risk for male infertility (odds ratio = 5.07, 95% CI = 1.29–23.29, p = .007). In silico analysis of SNPs that were specific to infertile men predicted that these SNPs lead to defective splicing by destroying or creating the potential binding site of splicing factors or causing alteration in predicted regulatory sequences. In the light of the above, our study suggests that the UBE2B gene is associated with male infertility in Indian men, hence, providing evidence for additional genetic factors for male infertility.

     Key words: Haplotype, SNPs, ubiquitin, ubiquitin-conjugating enzyme