Identification of 21 single nucleotide polymorphisms in human hepatocyte growth factor gene and association with blood pressure and carotid atherosclerosis in the Japanese population.
It has been suggested that circulating concentrations of hepatocyte growth factor (HGF) are increased in individuals with vascular endothelial damage, such as in hypertensive patients and subjects with atherosclerosis. Because the influence of genetic variation of HGF has not been examined, we identified single nucleotide polymorphisms (SNPs) in the HGF gene, and investigated the association between these SNPs and blood pressure or carotid atherosclerosis in the Japanese general population. We identified 21 SNPs in the HGF gene by direct sequencing in a test population of 32 Japanese subjects. Among them, considering allele frequency and linkage disequilibrium, three SNPs, C-1652T in the promoter, T43839A in intron 8, and T44222C in intron 9, were genotyped in 2412 members of the Japanese general population randomly selected from the residents in Suita city. None of the three SNPs were significantly associated with blood pressure. After adjusting for age, smoking habits, consumption of alcohol, and the presence of diabetes mellitus and dyslipidemia, female subjects with the T allele of T43839A had more severe carotid atherosclerosis compared to individuals with the A allele. This study provides the first evidence that HGF may be a candidate susceptibility loci that affects the progression of atherosclerosis in Japanese subjects.
Takiuchi
Shin
S
Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan. takiuchi@hsp.ncvc.go.jp
Mannami
Toshifumi
T
Miyata
Toshiyuki
T
Kamide
Kei
K
Tanaka
Chihiro
C
Kokubo
Yoshihiro
Y
Koyama
Yuko
Y
Inamoto
Nozomu
N
Katsuya
Tomohiro
T
Iwai
Naoharu
N
Kawano
Yuhei
Y
Ogihara
Toshio
T
Tomoike
Hitonobu
H
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011379:Prognosis; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D018608:Ultrasonography, Doppler
D017228:Hepatocyte Growth Factor