The prevalence of common CFTR gene mutations and polymorphisms in infertile Iranian men with very severe oligozoospermia

Abstract

Due to progress in infertility etiology, several genetic bases of infertility are revealed today. This study aimed to investigate the distribution of mutations in the CFTR gene, M470V polymorphism, and IVS8 poly T. Furthermore, we aimed to examine the hotspot exons (4, 7, 9, 10, 11, 20, and 21 exons) to find a new mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene among infertile Iranian men very severe oligozoospermia (<1 million sperm/mL ejaculate fluid). In the present case-control study, 200 very severe oligozoospermia (20-60s) and 200 fertile men (18-65s) were registered. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The M470V polymorphism was checked out by real-time PCR, and poly T and exons were sequenced. The F508del was the most common (4.5%) CFTR gene mutation; G542X and W1282X were detected with 1.5% and 1%, respectively. N1303K and R117H were detected in 0.5% of cases. F508del was seen as a heterozygous compound with G542X in one patient and with W1282X in the other patient. Also, in the case of M470V polymorphism, there are differences between the case and control groups (p=0.013). Poly T assay showed statistical differences in some genotypes. The study showed no new mutation in the exons mentioned above. Our results shed light on the genetic basis of men with very severe oligozoospermia in the Iranian population, which will support therapy decisions among infertile men.

Keywords: ACECR – Academic Center for Education, Culture, and Research; ARMA – Amplification-refractory mutation system; CBAVD – Congenital bilateral absence of the vas deferens; CF – Cystic fibrosis; CFTR gene; EDTA – Ethylenediaminetetraacetic acid; ICSI – Intracytoplasmic sperm injection; IVS8 poly T; M470V polymorphism; N1303K; R117H; SSCP – Single strand conformational polymorphism; very severe oligozoospermia.