ABSTRACT
BACKGROUND: Myocardial infarction (MI) is a complex multifactorial and polygenic disorder that is thought to result from an interaction between an individual's genetic makeup and various environmental factors. The purpose of this study was to investigate the association between a novel single nucleotide polymorphism in the prostacyclin synthase gene and MI. METHODS AND RESULTS: By the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we identified a single nucleotide polymorphism, C1117A, in exon 8. This nucleotide change did not cause an amino acid change in codon 373. We performed an association study of the polymorphism in 138 patients and 130 healthy control subjects. Multiple logistic linear regression analysis showed the genotype distributions were significantly different between the control group and the MI group (odds ratio, 2.12; 95% CI, 1.47-3.05, P =.04). The C/C genotype was found more frequently in the MI group than in the control group. CONCLUSIONS: We conclude that the C1117A polymorphism in exon 8 is associated with risk for MI and may be a genetic marker of MI in Japanese persons.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Intramolecular Oxidoreductases/genetics , Myocardial Infarction/genetics , Polymorphism, Single Nucleotide/genetics , Case-Control Studies , DNA Probes , Female , Genotype , Humans , Male , Middle Aged , Myocardial Infarction/enzymology , Polymerase Chain Reaction , Regression Analysis , Risk FactorsABSTRACT
The purpose of this study was to investigate whether an association exists between the promoter region of the prostacyclin synthase gene and essential hypertension (EH). Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a novel single nucleotide polymorphism (SNP), T-192G, in the 5'-flanking region. We performed an association study using the SNP in 200 patients and 200 controls. The allele frequency distribution in the two groups was not significantly different. Thus, this SNP in the PGIS gene is not associated with EH.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Hypertension/genetics , Intramolecular Oxidoreductases/genetics , Polymorphism, Genetic/genetics , Promoter Regions, Genetic/genetics , Adult , Alleles , Base Sequence/genetics , Female , Gene Frequency , Genetic Linkage , Genotype , Humans , Male , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Reference Values , Tandem Repeat SequencesABSTRACT
BACKGROUND: The Dopamine D3 receptor (DRD3) gene is thought to be involved in essential hypertension (EH) because dopamine inhibits renin secretion via this receptor and because disruption of the DRD3 gene increases blood pressure in mice. EH is a complex, polygenetic disease. Association studies using the candidate gene approach may provide important clues regarding the etiology of hypertension and define a basis for further genetic investigation. Therefore we examined the association between the Ser9Gly polymorphism in the DRD3 gene and EH. MATERIAL/METHODS: One hundred eighty-one patients with EH and 181 age-matched subjects with normal blood pressure were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction (PCR) was used to amplify the Ser9Gly polymorphic site in the DRD3 gene, and restriction fragment length polymorphism (RFLP) analysis of the PCR product was used to score the A and G alleles. Plasma renin activity and plasma aldosterone concentration were measured in untreated EH subjects. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium, and was not significantly different between the NT and EH groups. The frequencies of A and G alleles were 0.674 (244/362) and 0.326 (118/362) for the NT group and 0.688 (249/362) and 0.312 (113/362) for the EH group, respectively, and did not differ significantly between the two groups. The genotype did not influence the plasma renin activity and aldosterone concentration in untreated EH patients. CONCLUSIONS: The Ser9Gly polymorphism in the DRD3 gene are not associated with EH. However, our negative result does not exclude the possibility of another variant elsewhere in or near the DRD3 gene in EH.
