Thesis
ANALISIS DE HAPLOTIPOS DE LA REGION 5q 31-35 EN UNA POBLACION DE NIÑOS ASMÁTICOS MEXICANOS
Autor
M en C.Martínez Aguilar, Nora Ernestina
Institución
Resumen
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.