Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.
BACKGROUND
Hypertension is a major risk factor for cardiovascular disease. Although genetic 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. The purpose of the present study was to identify genetic variants that confer susceptibility to hypertension in Japanese individuals.


METHODS
A total of 5,734 Japanese individuals from two independent populations were examined: subject panel A comprised 2,066 hypertensive individuals and 824 controls; and subject panel B comprised 834 hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix).


RESULTS
The chi(2)-test revealed that 10 polymorphisms were significantly (P < 0.05) related to the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A-->G polymorphism (rs645106) of SDK1 and the C-->G polymorphism (rs12078839) of RABGAP1L were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the A-->G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition.


CONCLUSIONS
SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined.
Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
Mitsutoshi
M
Oguri
Kimihiko
K
Kato
Kiyoshi
K
Yokoi
Tetsuro
T
Yoshida
Sachiro
S
Watanabe
Norifumi
N
Metoki
Hidemi
H
Yoshida
Kei
K
Satoh
Yukitoshi
Y
Aoyagi
Yoshinori
Y
Nozawa
Yoshiji
Y
Yamada
D000368:Aged; D000409:Alanine; D044466:Asian People / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003545:Cysteine; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic
D015815:Cell Adhesion Molecules; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; C500479:RABGAP1L protein, human; C493091:SDK1 protein, human; D003545:Cysteine; D000409:Alanine; D005998:Glycine