**3.1.2 Genetic predilection**

Genetically determined deficiency of alpha1–protease inhibitor (A1PI) represents a proven genetic abnormality that predisposes to COPD(Ericksson,1964;Laurell & Eriksson,1963 as cited in Shapiro SD,2010). A1PI is inherited by codominant alleles on chromosomal segment 14q32.1. Early adult-onset emphysema associated with A1PI deficiency occurs most commonly with PiZZ (mutation in *SERPINA1* gene) phenotype. It is prevalent globally but most commonly found in whites of Northern European ancestry. Worldwide there are an estimated 116,000,000 carriers and 1,100,000 individuals with severe α1-AT deficiency.(Boas & Winnie,2011)

Linkage analysis studies in early-onset COPD families have identified another serine proteinase inhibitor(serpin E2) on chromosome 2 as a potential defect site(DeMeo etal.,2006;Wilk et al.,2009 as cited in Shapiro SD,2010). Twin and familial aggregation studies suggest that genetic factors likely influence variation in pulmonary function in nonsmokers, but may not necessarily increase the risk of developing a clinical diagnosis of COPD(ATS,2010).
