Rationale: Plasminogen activator inhibitor-1 (PAI-1) promoter variants and African ancestry both are associated with asthma. We evaluated the independent and joint effects of a gain of function (GOF) PAI-1 promoter variant and African ancestry on asthma odds.
Methods: Latinx subjects aged 8-21 years (1736 with asthma and 1747 healthy controls) from the GALA2 study were classified using African ancestry dichotomized at the 5th quintile. The variant (rs1799768) was dichotomized as wild type (GG) or risk allele (either heterozygous AG or homozygous AA). Using logistic regression, we evaluated the independent and joint effects of a PAI-1 GOF polymorphism and African ancestry proportion on asthma odds, controlling for confounding variables
Results: Subjects were 50% male, 13.2 (SD 3.5) years old, and had mean African ancestry proportion of 0.14 (SD 0.12). Compared to those with the wild type and African ancestry at the 1st-4th quintile, subjects at the top 5th quintile of African ancestry and the risk genotype had an increased odds of asthma (OR: 1.47, p = 0.003). Neither subjects with the risk genotype and at the lower quintiles (OR=1.07, P=0.39) nor those with the highest quintile of African ancestry and wild type genotype (OR 1.11, p=0.50) had an increased odds of asthma. In subgroup analysis, Puerto Rican subjects with the risk genotype and elevated ancestry retained this association (OR: 1.43, p = 0.035) but Mexican subjects with lower mean African ancestry did not.
Conclusions: A GOF promoter variant in PAI-1 and higher African ancestry proportion was synergistically associated with an increased odds of asthma
