Assessment of the genetic component of hypertension.
BACKGROUND
Although genetic epidemiologic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. We have now performed a large-scale association study to identify gene polymorphisms for reliable assessment of the genetic component of hypertension.


METHODS
The study population comprised 4853 unrelated Japanese individuals, including 2818 subjects with hypertension (1677 men, 1141 women) and 2035 controls (1011 men, 1024 women). The genotypes for 150 polymorphisms of 128 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.


RESULTS
Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking revealed that four polymorphisms (1648G-->A in ITGA2, -30G-->A in GCK, A-->G in SAH, and 1117C-->A in PTGIS) were significantly (P < .01) associated with hypertension. A stepwise forward selection procedure demonstrated that ITGA2, GCK, and PTGIS genotypes significantly affected the prevalence of hypertension. Combined genotype analysis of these polymorphisms yielded a lowest odds ratio of 0.47 for the genotypes of AA or AG for ITGA2, GA or AA for GCK, and CC for PTGIS, which were present in 1.1% and 2.0% of hypertensive and control individuals, respectively.


CONCLUSIONS
These results suggest that the genotypes for ITGA2, GCK, and PTGIS may prove reliable for the assessment of the genetic component of hypertension. Determination of the combined genotypes for these genes may contribute to personalized prevention of this condition.
Yamada
Yoshiji
Y
Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan. yamada@gene.mie-u.ac.jp
Matsuo
Hitoshi
H
Segawa
Tomonori
T
Watanabe
Sachiro
S
Kato
Kimihiko
K
Hibino
Takeshi
T
Yokoi
Kiyoshi
K
Ichihara
Sahoko
S
Metoki
Norifumi
N
Yoshida
Hidemi
H
Satoh
Kei
K
Nozawa
Yoshinori
Y
D000368:Aged; D044466:Asian People / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D000081410:Germinal Center Kinases; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D039421:Integrin alpha2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D000081410:Germinal Center Kinases; C056564:ITGA2B protein, human; D039421:Integrin alpha2; D003577:Cytochrome P-450 Enzyme System; D017346:Protein Serine-Threonine Kinases; C472456:PTGIS protein, human