engleski

Genotype distribution and methylation level of the polymorphic region in the serotonin receptor 2A gene promoter in German and Croatian healthy volunteers

Serotonin is a biologically active amine involved in regulation of many physiological functions through a variety of membrane-bound receptors, including the serotonin 2A receptor (HTR2A). The expression level of many genes is influenced by functional polymorphisms in their regulatory regions, but also through epigenetic mechanisms triggered by environmental factors, including DNA methylation of cytosine residues in CpG dinucleotides. HTR2A promoter region encompasses two single nucleotide polymorphisms (SNPs). SNP rs6311 (-1438 G/A) is located just next to the methylated -1439 cytosine and the presence of A, instead of G allele, results in loss of one CpG site. In SNP rs6306 (-1421 C/T), presence of T, instead of C allele, leads to the loss of another CpG site. The third, non-polymorphic, CpG site, close to the two SNPs, is located at 1522 bp upstream from the start codon. We have compared genotype distribution of the SNPs rs6311 and rs6306, as well as average methylation of three CpG sites in the polymorphic region of the HTR2A promoter between healthy volunteers from Munich, Germany and Zagreb, Croatia. Genotype distribution was very similar in German and Croatian groups for both, rs6311 (30% GG, 50% AG, 20% AA, and 31% GG 48.5% AG, 20.5% AA, respectively) and rs6306 (74% CC, 26% CT and 76% CC, 24% CT, respectively). As expected, average methylation was significantly (p<0.001) influenced by the number of CpG sites, reflecting different genotype combinations. In addition, average methylation was significantly (p=0.03) influenced by group affiliation, probably reflecting different environmental influences on Munich and Zagreb inhabitants. Bearing in mind the interaction between genetic and epigenetic events in determining the level of gene expression, our results indicate a need for consideration of DNA methylation levels when correlating genetic polymorphisms to gene expression/function in multicentric studies on populations with similar genetic background.

5-hydroxytryptamine; 2A receptor; methylation; polymorphysm; population

nije evidentirano