The Spectrum and Carrier Frequencies of Common Pathogenic Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Men from the General Population: The Role of Ethnicity

Abstract

Mutations in the CFTR gene, which cause the autosomal recessive disease cystic fibrosis, can also affect male fertility. The aim of this study was to investigate the spectrum and carrier frequency of common pathogenic CFTR variants among men from the general population, analyze ethnic differences, and assess associations with male fertility indicators. Male volunteers (n = 1895) from six cities in Russia and Belarus were analyzed for the carrier frequencies of 17 pathogenic CFTR variants and two polymorphisms, as well as semen quality and reproductive hormone levels. Heterozygous carriers of six pathogenic CFTR mutations, F508del, G542X, N1303K, 3849+10kbC>T, CFTRdele2,3, and R117C, and two polymorphisms, IVS9-5T and 5T-(12-13) TG, were identified, with cumulative frequencies of 2.06% and 6.65%, respectively. Significant ethnic differences were revealed in the spectrum and carrier frequencies of pathogenic CFTR variants among Slavs, Buryats, and Yakuts. Slavs exhibited a high proportion of heterozygous carriers of CFTR mutations (2.70%), whereas none were detected among Buryats and Yakuts. The highest carrier frequency for the CFTR polymorphism was observed among Slavs (8.35%), followed by Buryats (5.83%) and Yakuts (1.36%). No association was found between the carriers of identified CFTR variants and male fertility indicators. Thus, the spectrum and carrier frequency of genetic CFTR variants are determined by the ethnic composition of the population, providing a basis for ethnicity-specific screening of pathogenic CFTR variants.