Polymorphism of the C-reactive protein (CRP) gene is related to serum CRP level and arterial pulse wave velocity in healthy elderly Japanese

被引:40
作者
Morita, Akihiko
Nakayama, Tomohiro
Doba, Nobutaka
Hinohara, Shigeaki
Soma, Masayoshi
机构
[1] Nihon Univ, Sch Med, Div Mol Diagnost, Adv Med Res Ctr,Itabashi Ku, Tokyo 1738610, Japan
[2] Nihon Univ, Sch Med, Dept Med, Div Neurol, Tokyo 1738610, Japan
[3] Nihon Univ, Sch Med, Dept Med, Div Nephrol & Endocrinol, Tokyo 1738610, Japan
[4] Life Planning Ctr, Tokyo, Japan
关键词
C-reactive protein; arterial pulse wave velocity; single-nucleotide polymorphism; haplotype; diplotype;
D O I
10.1291/hypres.29.323
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The objective of this study was to clarify relationships between the C-reactive protein (CRP) gene and both the serum level of CRP and arterial pulse wave velocity (PWV), using haplotype analysis of healthy elderly Japanese. Five single-nucleotide polymorphisms (SNPs) of the human CRP gene (rs1341665, rs3091244, rs1800947, rs1130864 and rs1205) were used to genotype 315 healthy elderly Japanese subjects (mean age, 77.9 +/- 4.1 years; male/female ratio, 0.96). Linkage disequilibrium was analyzed for the five SNPs. The frequency of each haplotype and diplotype was estimated using the expectation/maximization (EM) algorithm. There were statistically significant associations between the CRP level and two CRP genotypes; the p value for the T allele of rs3091244 (CT+AT+TT vs. CC+CA+AA) was 0.002 (95% confidential interval [CI], 2.1-24), and the p value for the T allele of rs1130864 (TT+TC vs. CC) was 0.002 (95% Cl, 2.1-24). The only genotype that was significantly associated with arterial PWV was the C allele of rs1800947, with a p value of 0.039. The haplotype was constructed using rs1341665, rs3091244 and rs1800947, in that order. There was a significant association between the CRP level and the T-T-G haplotype, with a p value of 0.002 (95% Cl, 2.124). There was a significant association between arterial PWV and the C-C-C haplotype, with a p value of 0.039. We concluded that rs3091244, rs1130864 and the T-T-G haplotype are genetic markers for elevated basal CRP levels. rs1800947 and the C-C-C haplotype appear to be susceptibility markers for atherosclerosis, but this requires confirmation.
引用
收藏
页码:323 / 331
页数:9
相关论文
共 30 条
[21]   Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus [J].
Russell, AI ;
Graham, DSC ;
Shepherd, C ;
Roberton, CA ;
Whittaker, J ;
Meeks, J ;
Powell, RJ ;
Isenberg, DA ;
Walport, MJ ;
Vyse, TJ .
HUMAN MOLECULAR GENETICS, 2004, 13 (01) :137-147
[22]   Association study of calcitonin-receptor-like receptor gene in essential hypertension [J].
Sano, M ;
Kuroi, N ;
Nakayama, T ;
Sato, N ;
Izumi, Y ;
Soma, M ;
Kokubun, S .
AMERICAN JOURNAL OF HYPERTENSION, 2005, 18 (03) :403-408
[23]   Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene [J].
Szalai, AJ ;
McCrory, MA ;
Cooper, GS ;
Wu, J ;
Kimberly, RP .
GENES AND IMMUNITY, 2002, 3 (01) :14-19
[24]   Single nucleotide polymorphisms in the interleukin-6 gene associated with blood pressure and atherosclerosis in a Japanese general population [J].
Tanaka, C ;
Mannami, T ;
Kamide, K ;
Takiuchi, S ;
Kokubo, Y ;
Katsuya, T ;
Kawano, Y ;
Miyata, T ;
Ogihara, T ;
Tomoike, H .
HYPERTENSION RESEARCH, 2005, 28 (01) :35-41
[25]   Elevated C-reactive protein: a common marker for atherosclerotic cardiovascular risk and subclinical stages of pulmonary dysfunction and osteopenia in a healthy population [J].
Tomiyama, H ;
Okazaki, R ;
Koji, Y ;
Usui, Y ;
Hayashi, T ;
Hori, S ;
Yamashina, A .
ATHEROSCLEROSIS, 2005, 178 (01) :187-192
[26]   Influences of age and gender on results of noninvasive brachial-ankle pulse wave velocity measurement - a survey of 12 517 subjects [J].
Tomiyama, H ;
Yamashina, A ;
Arai, T ;
Hirose, K ;
Koji, Y ;
Chikamori, T ;
Hori, S ;
Yamamoto, Y ;
Doba, N ;
Hinohara, S .
ATHEROSCLEROSIS, 2003, 166 (02) :303-309
[27]   C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries [J].
Torzewski, J ;
Torzewski, M ;
Bowyer, DE ;
Fröhlich, M ;
Koenig, W ;
Waltenberger, J ;
Fitzsimmons, C ;
Hombach, V .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (09) :1386-1392
[28]   Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein [J].
Verma, S ;
Li, SH ;
Badiwala, MV ;
Weisel, RD ;
Fedak, PWM ;
Li, RK ;
Dhillon, B ;
Mickle, DAG .
CIRCULATION, 2002, 105 (16) :1890-1896
[29]   A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians [J].
Wolford, JK ;
Gruber, JD ;
Ossowski, VM ;
Vozarova, B ;
Tataranni, PA ;
Bogardus, C ;
Hanson, RL .
MOLECULAR GENETICS AND METABOLISM, 2003, 78 (02) :136-144
[30]   Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis [J].
Zee, RYL ;
Ridker, PM .
ATHEROSCLEROSIS, 2002, 162 (01) :217-219