ADAM33 Genotype as a Predictor of Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) is one of the most common causes of the respiratory conditions of adults in developed world. Smoking is the single most important risk factor in the development of COPD. However, genetic analyses have revealed evidence for linkage of COPD to a number of different chromosomal regions and for association with several candidate genes. Variation in A disintegin and metalloprotease 33 (ADAM33) gene is known to modify susceptibility to asthma traits. With this in mind we investigated the major asthma-associated ADAM33 SNPs for association with COPD in a well characterised New Zealand cohort of patients.
DNA and lung function measurements were collected from 639 patients aged between 28 and 77 years. Subjects were genotyped for the following SNPs in ADAM33: F+1, T_1 (Met-Thr) and ST+7. A COPD case group, defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 or higher (n=78) was compared to a supernormal group of non-COPD controls (n=83). Generalised Linear Models (GLM) and Logistic Regression were used to analyse the effect of genotypes on the COPD phenotype.
Our preliminary results show that the minor allele of SNP F+1 (grouped as a dominant genotype) was significantly associated with COPD phenotype in this group of patients. The odds ratio adjust for the effect of smoking, age and sex showed that participants with at least one minor allele of SNP F+1 were 1.8 times more likely to develop COPD compared to controls (OR = 2.2 95% CI: 1.1-4.35, P = 0.025). Genotypes for the other SNPs were not significant (P > 0.05)
Our initial genetic studies of a New Zealand patient group provide some evidence that variation in ADAM33 is associated with the COPD phenotype. We are continuing to investigate this gene by testing additional SNPs as well as exploring more phenotypes of lung function decline and response to medication.