Genetic insight into idiopathic male infertility in North India: Role of telomere maintenance genes.

BACKGROUND

Despite having a sizeable population and an increasing incidence of infertility, South Asia is still underrepresented in genetic studies of male reproductive health. In this area, little is known about idiopathic male infertility, which is frequently associated with subtle genetic variations. Both TERT (chromosome 5 [5p15.33]) and TERF2 (chromosome 16 [16q22.1]) genes are essential for spermatogenesis, as TERT is needed to maintain the telomere length, and TERF2 aids in chromosomal integrity and cell division. The purpose of this study is to fill a regional gap in molecular reproductive research by examining the relationship between telomere related genes TERT and TERF2, and idiopathic male infertility in the Jammu and Kashmir population of North India.

METHODS

In this study, 634 cytogenetically normal individuals were enrolled, out of which 220 were male infertile patients and 414 were fertile male controls. Individuals who had AZF microdeletions in their Y chromosome were excluded from the study. TaqMan assay was used to genotype two SNP's, TERT (rs10069690) and TERF2 (rs251796), and statistical analysis was carried out using various genetic models.

RESULTS

Under the dominant model, a significant association was observed between TERT SNP rs10069690 (T > C) (OR = 6.17;95 % CI:3.5-10.6; p < 0.05). A statistically significant connection was not seen between male infertility and TERF2 variant rs251796 (G > A) (p = 0.09)

CONCLUSIONS

This is the first report from North India to link male infertility to TERT gene polymorphism, suggesting that telomere maintenance may play a part in impaired spermatogenesis. These results highlight the significance of region-specific molecular screening in a larger population with increased sample size and may aid in advancement of predictive diagnosis for male reproductive health, particularly in South Asian populations that are undeserved.