Scientific Online Resource System

Varna Medical Forum

The IVS8(n)-T variant in the CFTR gene as a factor for male infertility

Mariya Levkova, Trifon Chervenkov, Mari Hachmeriyan, Lyudmila Angelova


The CFTR gene is one of the new candidate genes, which are thought to be required for normal spermatogenesis. Different variants in this gene, for example IVS8-(n)T polymorphism, could be associated with its impaired functioning and could lead to male infertility. The aim of this study is to investigate whether this variant is found among Bulgarian patients with male infertility.

We conducted molecular genetic testing of 25 men with sperm count below 5×106/mL in order to search for the presence of the IVS8(n)-T variant in their CFTR genes. The derived sequences were analyzed and compared to the human reference genome.

The median age of the participants with impaired spermatogenesis was 34.00 years. The median concentration of the sperm cells in the ejaculate was 0.30×106/ mL. After we conducted the molecular genetic analysis for variants in the CFTR gene, it was found that one participant (4.00%) was a homozygote for the 5Т/5Т variant, and another one (4.00%) was a heterozygote for the 5Т/7Т variant.  As for the remaining participants, 20 men (80.00%) were homozygotes for the wild 7Т variant, two (8.00%) – heterozygotes for the 7Т/9Т variant, and one (4.00%) – a homozygote for the 9Т/9Т variant. 

This study established the presence of the 5Т variant in the CFTR gene among the participants with impaired fertility due to azoospermia or severe oligozoospermia. This finding supports the role of polymorphisms in the CFTR gene and in particular the 5Т variant as a reason for male infertility.


CFTR; 5T variant; male infertility; spermatogenesis

Full Text


Савов, А., Генетични дефекти при пациентите с муковисцидоза в България. In spiro, 2011. 3.

Переновска, П., Муковисцидоза – диагноза и лечение. In spiro, 2011. 3.

Петрова, Г., et al., Пилотни данни от българския регистър на пациентите с муковисцидоза. Редки болести и лекарства сираци, 2016. 7(3): p. 11-16.

Castellani, C. and B.M. Assael, Cystic fibrosis: a clinical view. Cellular and Molecular Life Sciences, 2017. 74(1): p. 129-140.

Du, Q., et al., The CFTR M470V, intron 8 poly-T, and 8 TG-repeats detection in Chinese males with congenital bilateral absence of the vas deferens. BioMed research international, 2014. 2014.

Ghorbel, M., et al., Screening of ΔF508 mutation and IVS8‐poly T polymorphism in CFTR gene in Tunisian infertile men without CBAVD. Andrologia, 2012. 44: p. 376-382.

Jesus, T.T., et al., Aquaporin‐9 is expressed in rat Sertoli cells and interacts with the cystic fibrosis transmembrane conductance regulator. IUBMB life, 2014. 66(9): p. 639-644.

Jiang, L., et al., CFTR gene mutations and polymorphism are associated with non-obstructive azoospermia: From case-control study. Gene, 2017. 626: p. 282-289.

Lee, J.Y., et al., Role of genetics in azoospermia. Urology, 2011. 77(3): p. 598-601.

Liu, F., et al., Molecular structure of the human CFTR ion channel. Cell, 2017. 169(1): p. 85-95. e8.

Plaseska-Karanfilska, D., et al., Genetic causes of male infertility. Balkan Journal of Medical Genetics, 2012. 15(Supplement): p. 31-34.

Tamburino, L., et al., Molecular analysis of mutations and polymorphisms in the CFTR gene in male infertility. Reproductive biomedicine online, 2008. 17(1): p. 27-35.

Xu, W.M., et al., Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia. PLoS one, 2011. 6(5): p. e19120.

Yoon, J.C., et al., Male reproductive health in cystic fibrosis. Journal of Cystic Fibrosis, 2019. 18: p. S105-S110.



Font Size