SPINK5 and ADRB2 haplotypes are risk factors for asthma in Mexican pediatric patients

Abstract

Background: Asthma is one of the most common respiratory diseases worldwide, and the complexity of its etiology has been widely documented. Chromosome 5q31-33 is one of the main loci implicated in asthma and asthma-related traits. IL13, CD14 and ADRB2, which are located in this risk locus, are among the genes most strongly associated with asthma susceptibility. Objectives: This study evaluated whether single-nucleotide polymorphisms or haplotypes at 5q31-33 conferred risk for asthma in Mexican-Mestizo pediatric patients. Methods: We performed a case-controlled study including 851 individuals, 421 of them affected with childhood-onset asthma and 430 ethnically matched unaffected subjects. We used the TaqMan Allelic Discrimination Assay to genotype 20 single-nucleotide polymorphisms within IL5, RAD50, IL13, IL4, CD14, SPINK5, HTR4, ADRB2 and IL12B. Results: Although no association was detected for any risk allele, three SPINK5 haplotypes (GGCT: p = 6 × 10−6; AATC: p = 0.0001; AGTT: p = 0.0001) and five ADRB2 haplotypes (AGGACC: p = 0.0014; AGGAAG: p = 0.0002; TGAGAG: p = 0.0001; AGGAAC: p = 0.0002; AAGGAG: p = 0.003) were associated with asthma. Notably, the AGTT SPINK5 haplotype exhibited a male gender-dependent association (p = 7.6 × 10−5). Conclusion: Our results suggest that SPINK5 and ADRB2 haplotypes might play a role in the susceptibility to childhood-onset asthma.