Analysis of the selenoprotein P (rs7579) gene polymorphism and expression in patients with chronic pancreatitis combined with hypothyroidism

Abstract

Background. The specific role and place of genetic factors in the development of chronic pancreatitis and hypothyroidism, which determine the activity of glutathione antioxidant protection, have not been clarified. They are interconnected with changes in the fat and carbohydrate metabolism, and also affect the transport and signaling pathways of key nutrients for the work of the immune, endocrine and nervous systems. The purpose of the study is to investigate the selenoprotein P (SEPP1) (rs7579) gene polymorphism and expression in patients with chronic pancreatitis combined with hypothyroidism. Materials and methods. Forty-nine patients with chronic pancreatitis and hypothyroidism and 30 practically healthy individuals passed the screening stage. The SEPP1 (rs7579) gene polymorphism was determined by the polymerase chain reaction. Results. The study showed that out of 98 isolated alleles in patients with chronic pancreatitis and hypothyroidism and 60 alleles of the control group, the G allele of the SEPP1 gene (rs7579, 25191G/A) dominated over the A allele: in the examined patients — by 34.7 % (χ2 = 23.59; p < 0.001), in the practically healthy group — by 53.34 % (χ2 = 34.13; p < 0.001). At the same time, the relative frequency of individual genotypes, as well as wild-type and mutant alleles, probably did not differ between the experimental and control groups. The A allele of the SEPP1 gene (rs7579) slightly increases the risk of chronic pancrea­titis in the studied population, but non-significantly [risk ratio (RR) = 1.43; RR 95% CI (confidence interval): 0.91–2.26; odds ratio (OR) = 1.65; OR 95% CI: 0.88–3.08; p = 0.115]. Conclusions. In patients with chronic pancreatitis who are residents of Northern Bukovyna, mutation of the SEPP1 gene (rs7579, 25191G/A) in the homozygous state occurs with a frequency of 10.2 %, while it is absent in practically healthy people. In both groups, the G allele dominates over the A allele: in the examined patients — by 34.7 % (χ2 = 23.59; p < 0.001), in controls — by 53.34 % (χ2 = 34.13; p < 0.001). SEPP1 gene polymorphism (rs7579, 25191G/A) does not determine the risk of chronic pancreatitis in the population. However, the A allele increases the risk of hypothyroidism in chro­nic pancreatitis patients twice [OR = 2.0; OR 95% CI: 1.09–3.66; p = 0.023], with the lowest chances of its appearance in carriers of the G allele [OR = 0.50; OR 95% CI: 0.27–0.91; p = 0.023]. Mapping of the expression quantitative trait loci on both sides of the SEPP1 gene (rs7579) transcription start site evidenced 152 statistically significant cis-variants of rs7579 of the SEPP1 gene (SELENOP) associations with the expression of 20 genes in 35 different organs and tissues and 22 phenotypic traits.