Variants of <i>NOS3</i> gene polymorphism and lung function features in northerners

Abstract

Introduction. The study on polymorphic variants of the gene of endothelial nitric oxide synthase is important for understanding the genetic basis of the respiration system readjustments, particularly at adaptation to the North conditions. Aim. This research explored the occurrence of -786 T>S (rs2070744) polymorphism in the NOS3 gene and its correlations with indicators of the lung function in northern residents. Materials and methods. One hundred and twentyfive male volunteers, Caucasian by ethnicity of the Magadan Region, participated in continuous cross-sectional study. The mean age of the subjects was 41.4±1.3 yrs. The examinees underwent SNP testing of the -786 T>S (rs2070744) polymorphism of the NOS3 gene by polymerase chain reaction. Lung function flow-volume indicators was assessed using a spiroanalyzer KM-AR-01 Diamant-S (Russia), and a series of heart rate variability indicators were analyzed with the Varicard complex. Results. In the surveyed selection of northerners, the distribution of frequencies of alleles and genotypes of the NOS3 locus corresponded to the Hardy-Weinberg equilibrium law (χ2 =0.13; p=0.714). The NOS3 allele*T frequency was 64.57%, the NOS3*C allele concentration was 35.43%. The following genotype picture was observed in the examined male Northerners: -786 TT – 41.96%, -786 TC – 45.76%, and -786 CC – 12.28%. The analysis of the lung function revealed the worst impairments in volume-velocity variables (MEF25-75 84±1,2%) which were characteristic of those northern men (a group of subjects with the TT genotype) who did not have -786T >C (rs2070744) polymorphism of the NOS3 gene in their genotype as compared to the minor allele carriers (TT+CC genotype – MEF25-75 94±2,1%). In addition, heart rate variability indicators showed the parasympathetic link of the autonomic nervous system that prevailed in the same group. Conclusion. The studies allowed for the finding of reduced values of volume-velocity indices of the lung function in those male subjects whose genotype had no NOS3 allele*C (TT homozygotes). The findings were observed along with the prevailing parasympathetic link in the heart rate regulation, which may indicate compensatory adaptive mechanisms aimed at optimizing the lung function when adapting to the extreme climatic factors of the North. Therefore, we can assume that the TT genotype appears to be a selective advantage at adaptation to the cold. Following on from this, the TT genotype Northerners can be considered to be the most adapted for living in the conditions of the North.