Association of IL4 gene polymorphisms with asthma in North Indians

Asthma is a complex airway disorder, and a number of genetic loci have been found to be associated with asthma. The 5q31-33 region is one of the most important loci linked to asthma and atopic disorders. However, association studies with candidate genes in this region, such as IL4, were inconclusive, as both positive and negative results were obtained in several populations studied. The aim of our case-control study was to determine the association between IL4 and asthma in North Indians.

Polymorphisms in the promoter and a dinucleotide repeat in the 2nd intron in IL4 were genotyped by sequencing and GeneScan analysis, respectively, in ethnically matched, unrelated patients (n = 171) and controls (n = 128), following the guidelines of the American Thoracic Society.

The proximal promoter region of the IL4 gene was found to be invariant. Previously reported polymorphisms, -590 C/T and +33 C/T, were found to be absent in our population. The chi2 test using only large expected cell counts (more than 5% of the sample size) showed a significant association between allele size and disease status (chi2 = 38.08, d.f. = 6, p < 0.05). In addition, a significant difference was observed for the allele and genotype frequencies (p < 0.0005 and p = 0.0009, respectively) in the patient and the control groups using the Fisher-Freeman-Halton test.

Our studies indicate that the promoter of the IL4 gene is invariant in our population. The case-control studies on the CA repeat polymorphism in the 2nd intron of the IL4 gene have shown interesting results and indicate the need for further family-based studies.