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.

• 5q31-33 locus
• ADRB2
• asthma
• case-controlled study
• pediatric patients
• SPINK5

Acknowledgements

We thank Dr Michael Dean for reading the manuscript. The authors would like to acknowledge the patients and their families for their participation and we would like to thank the personal of Sequencing Unit, INMEGEN for their support.

Declaration of interest

This study was supported by a grant from Consejo Nacional de Ciencia y Tecnología, Mexico (CONACyT): 2011-C01-161936. The authors declare no conflicts of interest.