title: Polymorphisms and haplotypes of the regulator of G protein signaling-2 gene in normotensives and hypertensives.
abstract: Regulator of G protein signaling (RGS) proteins stimulate the GTPase activity of Galpha subunits of heterotrimeric G proteins, thereby negatively regulating G protein-coupled receptor signaling. RGS2, which preferentially alters Galphaq-mediated signaling, may be important for cardiovascular health, because knockout of RGS2 in mice is associated with altered smooth muscle relaxation and hypertension. In this study, we determined genetic variation in the human RGS2 gene by sequencing DNA in normotensive and hypertensive populations of whites (n=128) and blacks (n=122). We identified 14 single nucleotide polymorphisms and 2 two-base insertion/deletions (in/del; 1891 to 1892 TC and 2138 to 2139 AA). Although most of the genetic variants were found at low allelic frequency, in particular in coding regions, the 1891 to 1892 TC and 2138 to 2139 AA intronic in/del were in linkage disequilibrium and were associated with hypertension in blacks (P<0.05). We defined several haplotypes for the RGS2 gene, certain of which showed striking differences between whites and blacks. Additionally, 2 haplotypes had significantly different frequencies between hypertensive and normotensive black groups (P<0.05). We conclude that RGS2 is genetically conserved within coding regions but that the intronic in/del define ethnicity-specific haplotypes. Moreover, certain RGS2 variants that occur at greater frequency in hypertensive blacks may serve as ethnicity-specific genetic variants for this disease.
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Evan L
authors.initials: EL
authors.lastname: Riddle
authors.forename: Brinda K
authors.initials: BK
authors.lastname: Rana
authors.forename: Kenton K
authors.initials: KK
authors.lastname: Murthy
authors.forename: Fangwen
authors.initials: F
authors.lastname: Rao
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D017124:Conserved Sequence; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D020710:RGS Proteins; C087182:RGS2 protein, human