A case–control study of innate immunity pathway gene polymorphisms in Puerto Ricans reveals association of toll-like receptor 2 +596 variant with asthma

Abstract

BackgroundFor many years, African Dust Storms (ADE) has been thought to be associated with high prevalence of asthma in Puerto Rico (PR). Endotoxins (ENX) have been associated with ADE particulate matter (PM) and are known to promote pro-inflammatory responses in lung cells of susceptible individuals through the Toll-like receptor (TLR2/4) signaling pathways. Genetic variants are plausible contributors to such susceptibility. Therefore, we have evaluated a series of nine single nucleotide polymorphisms (SNPs) in TLR genes, which have been correlated positive and negatively to asthma prevalence and/or risk, in the Puerto Rican asthmatic population.MethodsThe following SNPs were evaluated in 62 asthmatics and 61 controls through Taqman® Real Time PCR Assay: TLR4 (+896A/G, +1196C/T, −6687A/G); TLR2 (+596C/T, −16934 T/A, +399A/G, +1349C/T) and CD14 (−159C/T, +1188C/G). Genotypes were assessed for asthma association employing an odds ratio (OR) analysis.ResultsMinor allele frequencies (n = 123) were determined for those variants as 0.07, 0.06, 0.35, 0.35, 0.37, 0.29, 0.04, 0.35 and 0.11, respectively. Two (+596C/T, +399A/G) TLR2 SNPs showed to be more represented in the asthmatic group by 89 % and 65 %, respectively. TLR4 SNP +896A/G analysis revealed only 1 G/G genotype (2 %) on the asthmatic group. The CD14 SNPs were similarly represented in the Puerto Rican population. Only the TLR2 +596 SNP was found to be significantly associated to asthma (OR = 3.24 for CT, 2.71 for TT) and particularly to females.ConclusionsThe identification of TLR SNPs will reveal potential candidates for gene-environment interactions in Puerto Ricans. As far as we know this is the first study to evaluate this type of TLR gene polymorphisms in Puerto Rican asthmatics, contributing to the current knowledge in the Hispanic population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0272-7) contains supplementary material, which is available to authorized users.

Genetic polymorphisms in pattern recognition receptors areassociated with allergic diseases through gene–gene interactions

“…Our results are consistent with studies in populations from Denmark, 30 Tunisia, 31 Egypt, 45 Korea, 46 and Japan 47 that did not find an effect of the TLR4/+896A/G polymorphism on the risk of asthma or atopy-related traits. In addition, similar results were obtained in both the Puerto Rican population 42 and a heterogeneous American cohort. 29 The lack of association between the TLR4/+896A/G polymorphism and asthma has also been confirmed by the latest metaanalysis.…”

“…21,27,[38][39][40][41] A significant correlation between the CD14/-159C/T polymorphism and asthma was not observed in another recent study among the Puerto Rican population, the population that exhibits the highest asthma prevalence of any racial or ethnic group. 42 On the other hand, other authors have reported a correlation of the CD14-159/TT genotype with a lower risk of developing asthma 17,31,35,43 or have even reported the opposite results. 32,33,44 In the present study, the genotype and allele frequency of the TLR4/+896A/G polymorphism did not significantly differ between the allergic patients and the controls.…”

“…30 Similarly, no association between the TLR2/-16934A/T polymorphism and asthma were found in the Puerto Rican population. 42 Interestingly, Kerkhof et al showed in their PIAMA cohort study that children with at least 1 A allele in TLR2/-16934 had a significantly lower risk of doctor-diagnosed asthma. 48 A similar, but statistically insignificant trend was observed in our analysis for atopy as well as for asthma and allergic rhinitis.…”

Association of polymorphisms in TLR2 and TLR4 with asthma risk

“…[ 20 ] Finally, 18 literatures were selected into the meta-analysis. [ 10 , 13 , 14 , 21 – 35 ] Figure 1 outlines our study selection process. The characteristics of studies included in the analysis were listed in Table 1 .…”

“…[ 12 ] During the past years, several studies about TLR gene polymorphisms and asthma have been conducted. [ 13 , 14 ] So, we conducted the update meta-analysis expecting to give a more determinately conclusion.…”