ANALISIS DE HAPLOTIPOS DE LA REGION 5q 31-35 EN UNA POBLACION DE NIÑOS ASMÁTICOS MEXICANOS

Abstract

Background: Asthma is a complex airways disorder, which involve multiple genetic, epigenetic and environmental factors. Numerous genetic studies have mapped asthma susceptibility genes to the region 5q31-35 in several populations. This region contains genes important in immune and pharmacologic response. The aim of the current study was to determine by a haplotype analysis, if 21 SNPs of nine candidate genes in the 5q 31-35 region interact to confer risk or protection to asthma in a Mexican pediatric population. Methods: We conducted a case-control haplotype association study. 415 patients and 437 controls were included. Genotyping analyses was performed using the TaqMan/qPCR allelic discrimination: 21 polymorphisms in 9 candidate genes. Results: Significant evidence for susceptibility was identified. Statistical significance for the different SNPs was maintained after 10 000 permutations. Finding six susceptibility sequences: one formed by SPINK5 SNPs (rs6892205, rs2303067, rs4349706) presented a haplotype association AGT protective sequence [OR=0.16 (CI 95% 0.06-0.45) p=0.000015159]. The most significative results were represented by SNPs in the ADRB2 gene (rs17778257, rs2053044, rs1042713, rs1042717, rs1042718, rs1042719) showing four risk sequences: AGGACC (p: 0.0012), TGAGAG (p: 0.00004), AGGAAG (p: 0.0001), AAGGAG (p: 0.0028), and one protective sequence: AGGAAC (p: 0.0017). Some differences by gender were observed. Conclusion: This haplotype study represents the relative interaction between different candidate genes in the region 5q 31-35 that confer risk or protection for development of asthma. The different SNPs studied were reported only in blocks of the same gene, but when associated with other genes lost significance.