title: Variants in genes involved in functional pathways associated with hypertension in African Americans.
abstract: Essential hypertension (HBP) is a complex trait with a substantial heritable component. The purpose of this study was to determine if variants in the G-protein coupled receptor Kinase-4 (GRK4), nitric oxide synthase-3 (NOS3), or angiotensin converting enzyme (ACE) genes are associated singly or through complex interactions, with HBP in African Americans aged 18-49 years. TaqMan Assays were used for genotyping the GRK4 and NOS3 variants. The ACE I/D variant was obtained by polymerase chain reaction and electrophoresis. Allelic association tests were performed for the five markers using PLINK. Logistic regression models were fitted to investigate associations between HBP status and the genetic markers. Multilocus analyses were also conducted. The study included 173 hypertensives and 239 normotensives, with stratification into obese and nonobese groups. The GRK4 A486V variant was negatively associated with HBP in the nonobese group (p = 0.048). The TT/CT genotype of GRK4 A486V was associated with decreased risk for HBP relative to the CC genotype after adjusting for age, sex, and body mass index (p = 0.028). Individuals having at least one NOS3 A allele and GRK4 R65L genotype GG had odds of HBP of 2.97 relative to GG homozygotes for NOS3 and GRK4 R65L. These results show very modest effects and do not fully replicate previous studies.
authors.affiliation: Department of Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Martinez Cantarin
authors.forename: Adam
authors.initials: A
authors.lastname: Ertel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Deloach
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.forename: Kathryn
authors.initials: K
authors.lastname: Scott
authors.forename: Trudy L
authors.initials: TL
authors.lastname: Burns
authors.forename: Bonita
authors.initials: B
authors.lastname: Falkner
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D049628:Body Size; D005260:Female; D054771:G-Protein-Coupled Receptor Kinase 4 / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D054643:INDEL Mutation / Q000235:genetics; D007438:Introns / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D054771:G-Protein-Coupled Receptor Kinase 4; D007703:Peptidyl-Dipeptidase A