A New Baltic Population-Specific Human Genetic Marker in the PMCA4 Gene

Abstract

Objectives: The PMCA gene family consists of 4 genes and at least 21 splice variants; among these, the Ca²⁺ ATPase 4 (PMCA4) gene encodes a plasma membrane protein abundantly expressed in several tissues, including the kidney, heart, and sperm. Knockout of PMCA4 causes infertility due to immotile sperm in mouse models. We therefore investigated variants in this gene for potential association with infertility in groups of Estonian (n = 191) and Latvian (n = 92) men with reduced sperm motility. Methods: All exons, exon-intron boundaries, 5′ and 3′ untranslated regions, and the promoter region of the PMCA4 gene were analysed by direct sequencing for a group of Estonian infertile men. Genotyping of guanine and adenine alleles of rs147729934 was performed, using a custom-designed TaqMan® probe for a group of Latvian infertile men as well as additional groups from Latvia and several groups of people with proven ethnicity from the Baltic region. Results: Although we did not identify any significant associations between variants in the gene and infertility, our results indicated that in all studied Latvian and Estonian groups the adenine allele of the variant rs147729934 was present at a higher frequency than expected. Analysis of additional samples indicated that the adenine allele of rs147729934 likely originated once in the modern-day Baltic or western Russia area, as the frequency of the minor adenine allele observed in this region is remarkably higher than that in the general European population. Conclusions: Our results revealed no significant difference in frequencies of genetic variants in PMCA4 gene between men with normal and those with reduced sperm motility. The adenine allele of the variant rs147729934 is potentially an informative tool for future population studies concerning ancient Baltic and Finno-Ugric history.

Sperm Ion Transporters and Channels in Human Asthenozoospermia: Genetic Etiology, Lessons from Animal Models, and Clinical Perspectives

“…Thus far, no gene mutations in PMCA4 have been identified in infertile patients. A study by Stavusis et al reported no significant association of PMCA4 gene variants in asthenozoospermic patients from Estonian and Latvian populations [ 140 ].…”