MedWire News: Ethnicity plays an important role in genetic susceptibility to chronic obstructive pulmonary disease (COPD), results of a meta-analysis show.

Writing in the American Journal of Respiratory and Critical Care Medicine, H Marike Boezen and colleagues from the University of Groningen in The Netherlands explain that smoking is the main cause of COPD, but genetic susceptibility is believed to play a determining role as only a relatively small proportion of smokers develop the disease.

However, they add: “Studies on the role of candidate genes and their polymorphisms in COPD development have so far produced ambiguous results.”

To investigate further, the researchers performed a literature search and identified 20 polymorphisms in 12 genes that were considered to be strong COPD-candidate genes.

The identified genes were each described in at least three published studies and are associated with the three main pathways of COPD development, namely the inflammatory, protease–antiprotease balance, and antioxidant pathways.

Analysis revealed that the interleukin-1 receptor antagonist gene (IL1RN) VNTR polymorphism was associated with an overall 1.7-fold increased risk for COPD.

Three polymorphisms in the transforming growth factor–β1 gene (TGFB1) were also associated with overall COPD risk, with rs2241712 and rs1982073 providing a slight protective effect while rs6957 was associated with an increased risk for COPD, at an odds ratio (OR) of 1.48.

In addition, the researchers found that the tumor necrosis factor-α (TNFA)–308 G/A polymorphism was associated with an increased risk for COPD and the glutathione S-transferase pi (GSTP1) I105V polymorphism was associated with a decreased risk for the disease, but only in Asian populations, with corresponding ORs of 2.01 and 0.69.

Most of the other candidate genes showed no significant association, or only a borderline association, with COPD risk.

The researchers conclude: “We showed that many candidate genes show no association with COPD after combining independent studies. For the majority of the genes more studies will be needed to reveal their role, especially in Asian populations.”

They add: “We show that ethnicity is very important in genetic studies, and therefore should always be taken into account, given that some associations show different directions for different populations.”

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