Genotypic distribution of polymorphisms within endosomal TLR receptor genes in Spanish healthy women

Objectives: Genetic variants of endosomal toll-like receptors (TLRs) have been associated to many infectious, autoimmune and inflammatory diseases, but there are few studies in Spanish population. The aim of this study was to describe the allelic and genotypic distributions of some single nucleotide polymorphisms (SNPs) of endosomal TLRs in Spanish healthy women and to compare them with those already published in other population groups. Methods: Nine SNPs were analyzed in 150 DNA samples from 150 Spanish, adult, non-related healthy females: TLR3 rs3775291 (Leu412Phe) and rs5743305 (g.4025T > A); TLR7 rs179008 (Gln11Leu) and rs5743781 (Ala448Val); TLR8 rs3764880 (Met1Val) and TLR9 rs187084 (−1486 T > C), rs5743836 (−1237 T > C), rs352139 (g.1174A > G) and rs352140 (Pro545Pro).Genotyping was performed by real time PCR and melting curve analysis in a LightCycler 480 system. A comprehensive research was carried out in the Medline database in order to compare the genotypic distributions of these SNPs with those previously published in other population groups. The comparative study was performed with the two tailed Fisher's test or the Yates continuity correction for the Chi-square test when appropriated. Results: All the polymorphisms analyzed in our population fulfilled the Hardy–Weinberg equilibrium. The rs5743781 variant of TLR7 was not found in homozygosity and rs352139 and rs352140 of TLR9 were in complete linkage disequilibrium. Our genotypic distribution was similar with those previously published in Spanish population. Significant differences were found in rs3775291 of TLR3 when compared with European and Asian populations, except for series with German and Japanese populations. Distribution of rs3764880 of TLR8 was similar to that observed in the Brazilian population of European ancestors, but statistically significant differences were found with Asian populations. Considering TLR9 SNPs, no differences were found when comparing our genotypic distributions with other Caucasian populations except for rs5743836 with the Swiss and Dutch series. Finally, TLR9 genotypic distributions were different when compared with most of the Asian populations, although no differences were found with some of them. Conclusions: A vast heterogeneity of genotypic distributions for genetic polymorphisms of endosomal TLRs has been reported. Our genetic distributions of SNPs in endosomal TLR are similar to other Spanish series previously published. As expected, most of the differences were found when comparing our distributions with Asian populations, but some differences were also found with other Caucasian populations. Therefore, according to the comparative results presented here, there are significant variations in genotypic distributions of TLRs in both interracial groups and within the same ethnic group. These differences prevent to assume a single determination of polymorphisms by ethnic groups, requiring the determination of polymorphisms in more circumscribed population groups.