Neuropeptide Y polymorphism increases the risk for asthma in overweight subjects; protection from atherosclerosis in asthmatic subjects - The cardiovascular risk in young Finns study

Aims: The role of neuropeptide Y (NPY) and its gene polymorphisms in the development of atherosclerosis has become increasingly evident. In asthma, NPY has been shown to be involved as immunomodulator. In this study, we investigated the role of two functional NPY polymorphisms, NPY-Leu7Pro (rs16139) and NPY-399C/T (rs16147) and obesity for the development of asthma as well as atherosclerosis in asthmatic and non-asthmatic subjects. Also, we measured heart rate variability (HRV) and NPY in serum since these might contribute through these polymorphisms to both diseases. Methods and results: Thousand hundred and seventy six Finnish young adults were genotyped and three groups (G1-G3) were formed based on the observed diplotypes. The NPY-Pro7 allele always co-existed with the NPY-399T allele indicating complete linkage disequilibrium. Here we show that overweight (BMI >= 25 kg/m(2)) was associated with 2.5-fold increased risk for asthma in subjects with the NPY-399T allele without NPY-Pro7 allele (G2, n = 716). Overweight was also associated with increased atherosclerosis determined by carotid intima media thickness (cIMT), but asthma seemed to be more significant determinant than overweight in determing cIMT having a decreasing effect. NPY concentration in serum was diplotype-driven (CI = 792.2(29.5), G2 = 849.0(18.9). G3 = 873.9(45.2) pg/ml) and correlated positively with cIMT in the group having NPY-Pro7 allele (G3, n = 142). However, the subjects with asthma had a negative NPY-cIMT relationship. Total HRV was increased in asthma and correlated negatively with cIMT irrespective of the NPY genotype. Conclusions: Overweight together with the NPY-399T allele without NPY-Pro7 allele was associated with increased risk for asthma. Atherosclerosis was decreased in subjects with asthma depending on the NPY genotype. The results reveal novel insights into the genetics and biology of the relationship of atherosclerosis and asthma. (C) 2012 Elsevier All rights reserved.