Khattri A, Bhushan S S, Sireesha V, Gupta N J, Chakravarty B N, Deendayal M, Prasad S, Singh L, Thangaraj K
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad Vasavi Medical and Research Centre, Vasavi Hospital, Hyderabad, India.
Int J Androl. 2011 Apr;34(2):173-82. doi: 10.1111/j.1365-2605.2010.01072.x.
Transition nuclear proteins (TNP1 and TNP2) are the major nuclear proteins that replace somatic histones during spermatogenesis. TNPs are required for the maintenance of normal spermatogenesis. Moreover, spermatogenesis was found to be compromised in both Tnp1 and Tnp2 null mice. As no study is available on the role of these genes in Indian infertile men, we have sequenced the entire TNP1 and TNP2 genes in 320 infertile men and 280 control fertile men drawn from two states in India. We identified 18 variants, including 8 previously known and 10 novel. Of the 10 novel variants, 3 were found only in azoospermic men, of which 2 (g.-688A>T in TNP1 and g.1030G>A in TNP2) were predicted to affect the transcription factor binding sites and therefore can cause deregulation of gene expression. Haplotype association analysis showed a significant omnibus association (omnibus χ(2) = 7.87, p = 0.0195) for the single nucleotide polymorphisms (SNPs) in the TNP1 gene with azoospermia. The frequency of the haplotype GCG (H3) was increased in azoospermic men (53.1%) compared with fertile men (43%; χ(2) = 7.964, p = 0.005). However, similar analysis of the TNP2 gene did not show any association with infertility. Furthermore, expression analysis of the TNP1 gene in obstructive azoospermic men showed that haplotypes of the TNP1 gene do not affect its expression level. Our results suggest that the individual SNPs of the TNP1 and TNP2 genes are not associated with infertility; however, the haplotype GCG of the TNP1 gene is a risk factor for azoospermia.
过渡核蛋白（TNP1和TNP2）是精子发生过程中取代体细胞组蛋白的主要核蛋白。TNP是维持正常精子发生所必需的。此外，在Tnp1和Tnp2基因敲除小鼠中均发现精子发生受损。由于尚无关于这些基因在印度不育男性中作用的研究，我们对来自印度两个邦的320名不育男性和280名对照可育男性的整个TNP1和TNP2基因进行了测序。我们鉴定出18个变异体，包括8个先前已知的和10个新的。在这10个新变异体中，有3个仅在无精子症男性中发现，其中2个（TNP1基因中的g.-688A>T和TNP2基因中的g.1030G>A）预计会影响转录因子结合位点，因此可能导致基因表达失调。单倍型关联分析显示，TNP1基因中的单核苷酸多态性（SNP）与无精子症存在显著的总体关联（总体χ(2)=7.87，p = 0.0195）。与可育男性（43%）相比，无精子症男性中GCG单倍型（H3）的频率增加（53.1%；χ(2)=7.964，p = 0.005）。然而，对TNP2基因的类似分析未显示与不育有任何关联。此外，梗阻性无精子症男性中TNP1基因的表达分析表明，TNP1基因的单倍型不影响其表达水平。我们的结果表明，TNP1和TNP2基因的单个SNP与不育无关；然而，TNP1基因的GCG单倍型是无精子症的一个危险因素。
