angiotensinogen and Hyperlipoproteinemia-Type-II

Topics: Amino Acid Sequence; Angiotensinogen; Apoproteins; Arteriosclerosis; Atrial Natriuretic Factor; Cloning, Molecular; DNA; Genetic Engineering; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type III; Hypertension; Myosins; Receptors, Cell Surface; Receptors, Lipoprotein; Sodium-Potassium-Exchanging ATPase

Recent large association studies have revealed associations between genetic polymorphisms and myocardial infarction and coronary heart disease (CHD). We performed a replication study of 10 polymorphisms and CHD in a population with familial hypercholesterolemia (FH), individuals at extreme risk of CHD.. We genotyped 10 polymorphisms in 2145 FH patients and studied the association between these polymorphisms and CHD in Cox proportional hazards models. We confirmed the associations between four polymorphisms and CHD, the rs1151640 polymorphism in the olfactory receptor family 13 subfamily G member 1 (OR13G1) gene (HR 1.14, 95% CI 1.01-1.28, P = 0.03), the rs11881940 polymorphism in the heterogeneous nuclear ribonucleoprotein U-like 1 (HNRPUL1) gene (HR 1.27, 95% CI 1.07-1.51, P = 0.007), the rs3746731 polymorphism in the complement component 1 q subcomponent receptor 1 (CD93) gene (HR 1.26, 95% CI 1.06-1.49, P = 0.01), and the rs10757274 polymorphism near the cyclin-dependent kinase N2A and N2B (CDKN2A and CDKN2B) genes (HR 1.39, 95% CI 1.15-1.69, P < 0.001).. We confirmed previously found associations between four polymorphisms and CHD, but refuted associations for six other polymorphisms in our large FH population. These findings stress the importance of replication before genetic information can be implemented in the prediction of CHD.

Topics: Adult; Angiotensinogen; Cholesterol; Cohort Studies; Coronary Disease; Female; Genes, p16; Genetic Predisposition to Disease; Genotype; Heterogeneous-Nuclear Ribonucleoproteins; Humans; Hyperlipoproteinemia Type II; Male; Membrane Glycoproteins; Middle Aged; Nuclear Proteins; Polymorphism, Genetic; Receptors, Complement; Receptors, Odorant; Risk Factors; Transcription Factors

Familial hypercholesterolemia is characterized by high plasma low-density lipoprotein cholesterol levels and premature coronary heart disease. Despite the monogenetic origin of familial hypercholesterolemia, the incidence of coronary heart disease varies considerably among patients, which is only partly explained by classical risk factors. Hypertension is an important risk factor for coronary heart disease that is associated with angiotensinogen levels. Therefore, we analyzed the angiotensinogen gene as a modifier gene for coronary heart disease risk in patients with familial hypercholesterolemia.. In a cohort of 1785 familial hypercholesterolemia patients, we reconstructed five frequent haplotypes of the angiotensinogen gene, based on four polymorphisms. The five haplotypes cover approximately 98% of the genetic diversity accounted for by these four polymorphisms. The associations between the haplotypes and coronary heart disease were analyzed with the haplo.stats program, adjusted for age, sex and smoking.. Patients homozygous for the C allele of the 4072 T>C polymorphism had a 34% increased coronary heart disease risk (P = 0.017) compared to patients homozygous for the T allele. Haplotype H3, consisting of the minor allele of the 4072T>C polymorphism and the major alleles of the other polymorphisms, had a frequency of 15% and was associated with a 45% increased coronary heart disease risk (P = 0.006) compared to the wild-type haplotype H1.. We conclude that genetic variation in the angiotensinogen gene contributes to coronary heart disease risk in patients with familial hypercholesterolemia.

Topics: Adult; Alleles; Angiotensinogen; Coronary Artery Disease; Female; Haplotypes; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Polymorphism, Genetic