ADAM33 gene polymorphisms identified to be associated with asthma in a Chinese Li population

Abstract

Abstract. A disintegrin and metalloprotease 33 (ADAM33)is an asthma susceptibility gene that has been proven to be present in certain human populations. The Li population is a minority ethnic group, most of whom maintain a distinctive lifestyle on Hainan Island in southern China. To the best of our knowledge, no previous study has established whether ADAM33 polymorphisms are associated with asthma in the Li population. Therefore, the ADAM33 polymorphisms in a Li population were investigated in the present study. A total of 150 asthma patients and 100 healthy subjects were enrolled in the present study, and their DNA samples were evaluated to analyze eight single-nucleotide polymorphisms (SNPs) on the ADAM33 gene. Asthma patients were subcategorized into low and high severity groups, and their SNP data were compared with the data of the control subjects. Single-marker and haplotype association was analyzed to demonstrate the association between ADAM33 SNPs and asthma using multiple genetic statistic tests. The results indicated significant differences in allele frequencies at the SNPs rs44707/T2 (P=0.008), rs2787094/V4 (P=0.028) and rs2280089/T+1 (P=0.021) between asthma patients and control subjects. The SNP rs44707/T2 was also found to be associated with the high severity group (P=0.024), although SNPs rs2787094/V4 were associated with the low severity group (P=0.019). Two haplotypes, GGAGAGT and GAAGGGT, were significantly associated with asthma (P=0.003 and 0.008, respectively). To the best of our knowledge, this is the first time that SNP rs2280089/T+1 has been reported to be associated with asthma in an Asian population. These data confirm that ADAM33 polymorphisms are associated with asthma susceptibility in the Li population and confirm the uniqueness of the Li minority population within China. IntroductionAsthma is a chronic inflammatory disease of the airway. More than 100 million people across the globe suffer from this disorder (Global strategy for asthma management and prevention; http://www.ginasthma.org). Airway inflammation, bronchial hyperresponsiveness (BHR), and reversible airflow obstruction are the primary characteristics of asthma. Among these, airway inflammation is most closely associated with the clinical symptoms. Currently, genetic and environmental factors have been found to be involved in the generation of asthma pathologies. Thus, the potential contribution of genetic factors is considered to be an interesting area of clinical and basic research.The A disintegrin and metalloprotease 33 (ADAM33) gene is an asthma susceptibility gene, which was first reported by Van Eerdewegh et al (1). The ADAM33 gene is mapped to the short arm of chromosome 20p13 in the human genome, and is predominantly expressed in airway smooth-muscle cells and lung fibroblast cells, but not in epithelial cells, T cells or inflammatory leukocytes (2-6). ADAM proteins are involved in cell-cell and cell-matrix interactions (5), cell migration (2,3), cell-cell adhesion and signal transduction (4). The following are c...

Evaluation of ADAM33 gene’s single nucleotide polymorphism variants against asthma and the unique pattern of inheritance in Northern and Central Punjab, Pakistan

“…However, a strong LD among these SNPs was not observed, contrary to the findings in our population. Another recent study on a Chinese Li23 population reported the significant association of rs2280089, and the non-significant association of rs2280091 with susceptibility to asthma. The same study also predicted a low LD between the SNP variants in the Li population.…”

“…The allele and genotype frequencies of these variants were also found to be non-significant after stratification based on age, gender, family history of asthma in asthmatics, and urban/rural/semi-urban population. Despite the reported significant associations of these SNPs with asthma in multiple populations, no significant association has been identified in sub-ethnic populations of the same origin 8,14,16,23. A recent study based on 2 cities of Pakistan (Islamabad and Lahore) reported a protective role of rs2280091 against asthma in a Pakistani population 24.…”

Interaction between early-life pet exposure and methylation pattern of ADAM33 on allergic rhinitis among children aged 3–6 years in China

“…ADAM33 is expressed in the smooth muscle, myofibroblasts, and fibroblasts of asthmatic airways, thus the function of this protein might be involved in the airway remodeling [ 35 ]. Various lines of evidence from previous human and animal studies have indicated that the expression level of ADAM33 was upregulated during acute or chronic lung inflammation [ 36 ]. Even though the existence of this functional link between ADAM33 and allergic airway inflammation, its role in the pathophysiology of AR is still to be clarified.…”

Interaction between early-life pet exposure and methylation pattern of ADAM33 on allergic rhinitis among children aged 3-6 years in China

“…ADAM33 is expressed in the smooth muscle, myo broblasts, and broblasts of asthmatic airways, thus the function of this protein might be involved in the airway remodeling (35). Various lines of evidence from previous human and animal studies have indicated that the expression level of ADAM33 was upregulated during acute or chronic lung in ammation (36). Even though the existence of this functional link between ADAM33 and allergic airway in ammation, its role in the pathophysiology of AR is still to be clari ed.…”