Genetic diversity of the IL‐4, IL‐4 receptor and IL‐13 loci in mestizos in the general population and in patients with asthma from three subpopulations in Mexico

Abstract

Asthma is an inflammatory airway disease characterized by increased serum IgE levels, mucus hypersecretion and infiltration of inflammatory cells, and is a multifactorial disease that exhibits genetic heterogeneity. Polymorphisms in the interleukin-4 (C-590T), interleukin-4 receptor (ile50val and gln576arg), and interleukin-13 (arg130gln) genes have been described as susceptibility alleles for asthma. This study was designed to determine whether asthma susceptibility is influenced by genotypic and allelic distribution of the above polymorphisms in three Mexican subpopulations. Four hundred and thirty-seven subjects from three Mexican subpopulations were classified into two groups: general population and affected/unaffected and genotyped for the above polymorphisms. We compared the distributions of the loci in the groups. In addition, we undertook association analysis between these loci and asthma phenotype in each affected/unaffected group, and determined Nei's genetic distance between the three subpopulations. The allelic and genotypic distributions of the polymorphisms differed between the three subpopulations. There was no association between any of the polymorphisms and asthma phenotype. However, there was a differential distribution of haplogroups (P < 0.0001) between the affected and the unaffected groups from the subpopulations of Jalisco and Guerrero. The genetic distribution of the four polymorphisms in the subpopulations did not influence susceptibility to asthma. Furthermore, the difference in the prevalence of asthma in these subpopulations is not attributable to the genetic background for the four polymorphisms analysed. However, haplogroup analysis suggests that the interaction of the polymorphisms and other predisposing alleles leads to the expression of the clinical phenotype.

Single Nucleotide Polymorphism in the Promoter of the Human Interleukin-13 Gene Is Associated with Asthma in Malaysian Adults

“…However, the frequencies for the C- and T-alleles in this site were similar to that reported in the African American population [22]. For the SNP at position 4257G>A of the human IL-13 gene, allele frequencies for the G-allele in Malaysian asthmatics and control subjects recruited in this study were found to be similar to the frequencies reported for the Koreans [28] and the Mexicans [25]. In comparison to the Malaysians, the Dutch population reported a higher frequency for the 4257G allele compared to the 4257A allele in both asthmatics and control subjects [1].…”

“…However, no significant association between genotype and allele frequencies between this SNP and asthma was found. These results matched the findings from similar studies done on the Dutch [1], Chinese [23], and Mexican [25] populations but differed from studies done on the British, Japanese [21, 26], and Korean [27, 28] populations. Association analyses with the polymorphism at site 4257 in the IL-13 gene produced varied results [1, 8, 21, 26, 27].…”

SPINK5andADRB2haplotypes are risk factors for asthma in Mexican pediatric patients

“…Despite the wide replication of results suggesting associations between asthma and IL4 and IL13, previous studies that included adult Mexican patients detected no distribution differences in IL4 C590T and IL13 Arg130Gln between asthmatic cases and controls [18,19]. The lack of association of highly reproduced polymorphisms in many ethnic groups highlights the genetic heterogeneity underlying asthma and emphasizes the need for investigation of candidate genes in each population.…”

“…When we compared cases and controls, no statistically significant differences were observed in the frequencies of 20 SNPs located at 5q31-33. A few Mexican studies have investigated genes located at 5q31-33; studies including Mexican adults or children were not able to replicate the association of IL13 and IL4 SNPs with asthma [18,19,27]. These findings, which are in contrast to results from investigations of other populations, may be due to the complex genetic background of the Mexican population, which stems from the mixture of races during conquest, but also could be due to differential interaction between genotype and environmental background in these populations [2,28].…”

Association of interleukin‐13 C‐1112T and G+2044A polymorphisms with asthma: A meta‐analysis

“…The electronic literature searches of the Medline and CNKI databases for studies on the association of the IL13 C‐1112T and/or G+2044A polymorphisms with asthma identified 44 publications (23 on C‐1112T, 38 on G+2044A and 17 on both). After review of the full‐text articles, 26 publications were excluded from the meta‐analysis for the following reasons: six did not report detailed genotype frequencies, 18,22,36–39 six were multiple publications on the same study populations, 26,40–44 four had family‐based study designs, 20,45–47 four did not report case–control studies, 19,21,48,49 and six were low quality publications (quality score ≤4) 50–55 . Because the publications of Donfack et al 56 .…”