Genetic variations of regulator of G-protein signaling 2 in hypertensive patients and in the general population.
OBJECTIVE
Mice deficient in the regulator of G-protein signaling 2 (RGS2) exhibit a strong hypertensive phenotype. We studied whether genetic variations in RGS2 are implicated in hypertension or other phenotypes in Japanese hypertensive individuals and the general population.


METHODS
We sequenced all exons of RGS2 and the promoter region in 953 and 48 hypertensive individuals, respectively. Genotyping by the TaqMan polymerase chain reaction method was performed for six missense or frameshift mutations and common single nucleotide polymorphisms in the general population, with a sample size of 1872 individuals (862 men and 1011 women).


RESULTS
We identified five novel missense mutations (Q2L; n = 2, Q2R; n = 1, M5V; n = 1, R44H; n = 2, Q78H; n = 1) and one novel frameshift mutation (1925-1926insT; n = 2) in a heterozygous state, in addition to 33 variations including five common single nucleotide polymorphisms. Six missense/frameshift mutations and three common single nucleotide polymorphisms (-638A > G, 1026T > A, 1891-1892delTC) were successfully genotyped in the general population. Mutations Q2L (n = 2), M5V (n = 1), and 1925-1926insT (n = 2) were only identified in hypertensive subjects. Six out of seven individuals with the R44H mutation, which occurs in the amphipathic alpha-helical domain of RGS2, had hypertension. The results showed a significant association of two common single nucleotide polymorphisms, 1026T > A [TT versus TA + AA: odds ratio (OR) 1.33; 95% confidence interval (CI) 1.02-1.74; P = 0.035] and 1891-1892delTC (I: insertion allele, D: deletion allele, II versus ID + DD: OR 1.47; 95% CI 1.09-1.97; P = 0.012), with hypertension in women by multivariate logistic regression analysis.


CONCLUSIONS
Our results suggest that genetic variations in RGS2 contribute partly to the hypertensive phenotype.
Yang
Jin
J
Divisions of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka, Japan.
Kamide
Kei
K
Kokubo
Yoshihiro
Y
Takiuchi
Shin
S
Tanaka
Chihiro
C
Banno
Mariko
M
Miwa
Yoshikazu
Y
Yoshii
Masayoshi
M
Horio
Takeshi
T
Okayama
Akira
A
Tomoike
Hitonobu
H
Kawano
Yuhei
Y
Miyata
Toshiyuki
T
D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D005828:Genetics, Population; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D020125:Mutation, Missense; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary
D002352:Carrier Proteins; C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins