The Association Between Single Nucleotide Polymorphisms Of Inflammation Makers And The Arterial Stiffness And Left Ventricular Structure

Aim:Arterial stiffness and left ventricular hypertrophy are the most important cause of essential hypertension and its cardiovascular diseases complication, also the main pathology phenomena of essential hypertension. It was reported that inflammation status correlate with arterial stiffness, but the role of inflammation in the development of arterial stiffness is still unclear. This study analyze the distributions of inflammation markers'single nucleotide polymorphisms (SNPs) in American youth, the correlations between the SNPs with the phenotypes of arterial stiffness and left ventricular structure, to discover the genetic role of inflammation in the onset of arterial stiffness.Methods:A total of 926 normotensive adolescents including whites and blacks (17.6±3.3 yrs,43.4% blacks) were recruited in Augusta area. Participants were subjected to a stress-protocol including three tasks (a 5 minute mental math, competence interview, a 3 minute video game challenge, and a 3 minute cold pressor test). Blood samples were obtained before and after the tasks, and SNPs of interleukin-6, interleukin-6 receptor alpha, C-reactive protein, E-selectin, P-selectin, vascular cell adhesion protein-1, and intercellular Adhesion Molecule-1 were genotyped. The blood pressure and the phenotype of arterial stiffness were measured before and after the tasks, and the left ventricular structure was measured by 2D directed M-mode echocardiograms. The correlations between the genotypes of inflammation markers and phenotypes of arterial stiffness and left ventricular structure were carried out by SPSS15.0.Result: in this study, the African Americans subjects (AA) have higher baseline systolic blood pressure (BP) than European Americans subjects (EA) (114.0±10.9 vs. 10.2±10.0 mmHg, p<0.0001), and the BP of some AA's reach the criteria of prehypertension (>120mmHg,<140mmHg). AA's carotid-radial PWV (cr-PWV) were higher than EA's (6.7±1.0 vs. 6.3±1.1,p<0.0001), total peripheral resistance index (TPX) of AA's were higher than EA's (28.6±8.4与26.1±7.6,p<0.0001). The indexes of left ventricular (LV) thickness were higher in AA's than in EA's, but the left ventricle internal dimension in systole (LVIDs) and cardiac index (CI) were lower in AA's than in EA's.Male subjects have higher baseline systolic BP than female (115.3±10.4 vs.108.9±9.8 mmHg,p<0.0001), and the BP of some males reach the criteria of prehypertension (>120mmHg,<140mmHg). Male subjects have higher stress systolic BP (126.5±12.1 vs. 115.8±0.8 mmHg,p<0.0001), and higher stress TPX (31.7±8.4 vs.29.6±7.8,p<0.0001) than female, but stress CI and stress high rate lower than female. Male have higher indexes of left ventricular (LV) thickness than female.For C-reactive protein (CRP), The C allele carriers of G1059C have lower diastolic BP, lower△HR, and higher interventricular septum thickness in diastole (IVSd), higher left ventricular mass index (LVMI) than G allele carriers. The A allele carriers of-717A>G have lower baseline pulse pressure (PP), lower carotid-foot PWV, lower carotid-radial PWV than G allele carriers.-286C>T>A was correlated with arterial stiffness and LV structure.For interleukin-6 (IL6), The CC genotype carriers of G-174C have lower carotid-foot PWV than CG/GG carriers.For gp130, the CC genotype carriers of rs3729961 have higher TPX than CG/GG carriers.For IL6 receptor alpha, D358A and rs4072391 were correlated with baseline PP. The CCT(212) haplotype carriers have higher baseline CI, but lower baseline TPX, than LVMI, LVPWD, IVSD, IVSS, RWT than CTT(222) haplotype carriers.For P-selectin, The 290Asn allele carriers of Ser290Asn have higher carotid-foot PWV and carotid-radial PWV than other carriers. The C allele carriers of rs2244529 have lower carotid-foot PWV than TT carriers.For intercellular Adhesion Molecule 1 (ICAM-1), The Arg241Arg and Gly241Arg carriers of Gly241Arg have lower carotid-foot PWV than Gly241Gly carriers.For vascular cell adhesion protein-1 (VCAM-1), The CC genotype carriers of Asp693Asp have higher carotid-foot PWV than CT and TT carriers.The synergetic effects of Ser290Asn (SELP), Gly241Arg (ICAMl) and Asp693Asp (VCAM1) could explain a greater portion (3.6%) of the foot PWV than any single SNPs. Conclusion:In American youth, AA subjects have higher BP level and arterial stiffness, and lower LV function, compare to the EA subjects, which could be explained by the genetic effect in difference Ethnic population.In American youth, male subjects have higher BP level and lower LV function, compare to the female subjects, which could be explained by the genetic effect in gender difference.In American youth, the G1059C,-717A>G,-286C>T>A SNPs of CRP were correlated with arterial stiffness and LV hypertrophy. The G-174C (IL6), rs3729961(gp130), D358A(IL6R), and rs4072391(IL6R) were correlated with arterial stiffness.P-selectin (Ser290Asn and rs2244529), ICAM-1 (Gly241Arg) and VCAM-1 (Asp693Asp) were predisposing genes for arterial stiffness.In conclusion, this study showed that the genetic variations of inflammation markers and adhesion molecules affect the development of arterial stiffness. To explore the SNPs of these molecules may help understand the pathophysiologic process in arterial stiffness.