title: Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses.
abstract: We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.
authors.affiliation: Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Bansal
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, UP, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Jaiswal
authors.affiliation: Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Nishi
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, UP, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Singh
authors.affiliation: Lab for Molecular Reproduction and Genetics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Rima
authors.initials: R
authors.lastname: Dada
authors.affiliation: Departmentof Urology, King George's Medical University, Lucknow, India.
authors.forename: Satya Narayan
authors.initials: SN
authors.lastname: Sankhwar
authors.affiliation: Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.affiliation: Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D041322:Chromosomes, Human, Y / Q000737:chemistry*; D005298:Fertility / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D044469:Racial Groups; D017384:Sequence Deletion; D013076:Sperm Count; D013091:Spermatogenesis / Q000235:genetics