Haplotype analysis of ADAM33 polymorphisms in asthma

Abstract

Background & objectives:ADAM33 is implicated as a potentially strong candidate gene for asthma and bronchial hyper-responsiveness. Many polymorphisms of ADAM33 have been studied along with ADAM33 expression in various cells of the lungs. Haplotype analysis also showed association with asthma in different populations across the world. Therefore, the aim of this study was to perform a comprehensive screening of ADAM33 polymorphisms in adult patients with asthma.Methods:Thirty five polymorphisms of ADAM33 were genotyped in 55 patients with asthma and 53 controls. The association of single nucleotide polymorphisms (SNPs) and haplotypes with phenotypes of asthma was analysed.Results:The genotype, minor allele frequency, odds ratio and Hardy–Weinberg equilibrium did not show any significant difference among cases and controls. No association was found between SNPs of ADAM33 with the severity of asthma. Correlation analysis of ADAM33 SNPs to the phenotypes, based on clinical variables and allergen sensitization, did not show significant difference. Haplotype analysis showed that rs2280090 and rs2280091 were associated with asthma in the patient group.Interpretation & conclusions:Haplotype analysis showed an association of the two SNP variations with asthma. These SNPs lead to amino acid change and are prone to phosphorylation, which may affect expression levels and protein function of ADAM33 and asthma susceptibility.

Allergic diseases in India – Prevalence, risk factors and current challenges

“…Candidate gene studies in India are summarized in Table 1. The established risk factor ADAM33 was confirmed in both North and South Indian populations 122–124 . Polymorphisms in transcription factors TBX21 and FOXO3a are associated with asthma development and severity 125,126 …”

“…The established risk factor ADAM33 was confirmed in both North and South Indian populations. [122][123][124] Polymorphisms in transcription factors TBX21 and FOXO3a are associated with asthma development and severity. 125,126 In an Indian study of 33 Th2 relevant genes population, SNPs in IRF2, IFNγR2, IL6, STAT4 and IL4RA were associated with asthma.…”

ADAM33′s Role in Asthma Pathogenesis: An Overview

“…SNPs are the most frequent type of genetic variation found among individuals, and they are strongly linked to susceptibilities to many diseases [2]. The University of California Santa Cruz Genome Browser indicates 90 SNPs observed within the ADAM33 gene [31]; nevertheless, the literature indicates the total number of these SNPs exceed 340, with 35 indicated in the literature as possibly associated with asthma [32].…”

“…Northern Indian [34], German [34], Icelandic [34], and Chinese [34] Associated with lung function deterioration in early life [34] Q1, Asian in general [9], Chinese Han [9], adults in general [9], and Caucasian children [9] Homozygous for minor alleles of SNP Q-1 (CC), rapid decline in FEV1 of 9.6 mL/year [34] T2, Asian in general [9,35], children in general [9], West Bengal, and India [38] Associated with the type 2 endotype of asthma [20] S + 1 South India [41] S1 West Bengal, India [38] Interaction between prenatal exposure to cigarette smoke in relation to the development of BHR [43] Associated with respiratory impedance at the age of 8 [43] S2 Jordanian, British, Europeans, Black Americans, White Americans, Hispanic Americans, and Thai [34,35] Interaction between prenatal exposure to cigarette smoke in relation to the development of BHR [43] associated with predicted FEV1% [43] ST + 4 Children in general [9] ST + 7 US White and Dutch White [10] T1 Asian children [32], West Bengal, India [38], and Iraqi Arab population [14,39] An allele associated with higher eosinophil count, increased airway hyperresponsiveness [36], increased inflammatory cell counts, and a decline in lung function in patients with COPD [32] Site corresponds to the domain involved in intracellular signaling [32] V4 Caucasian in general [9], adults in general [9], Jordanian children [34], United States/United Kingdom combined children [34], United Kingdom children…”

“…Such analyses are particularly advantageous due to their potential to capture causal variants more accurately than individual SNPs and may themselves be potent variants influencing disease [32,44].…”