Copyright © 2001 by the European Society of Cardiology.
The interleukin-6 –174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men
a Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Department of Medicine, Royal Free and University College London Medical School, London, U.K.
b MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, Medical College of St. Bartholomew's Hospital, London, U.K.
revised February 20, 2001; accepted February 21, 2001
Abstract
Aims Inflammation is a key component of coronary heart disease, and genes coding for cytokines are candidates for predisposing to coronary heart disease risk. We have examined the effect of two polymorphisms (–174G>C and –572G>C) in the promoter of the interleukin-6 (IL-6) gene on risk of coronary heart disease, and on intermediate risk traits including fibrinogen and systolic blood pressure, in 2751 middle-aged healthy U.K. men.
Results The –174C allele (frequency 0·43, 95% CI 0·42–0·44) was not associated with significant effects on fibrinogen levels, but was associated with a significantly (P=0·007) higher systolic blood pressure (mean mmHg (95% CI): GG=135·5 (134·3–136·7); GC=137·9 (136·9–138·9); CC= 138·0 (136·3–139·8)). This effect was of similar magnitude in smokers and non-smokers, and was greater in men in the top two tertiles of body mass index (>24·86kg.m–2) than in those in the bottom tertile. Compared to those with the genotype GG, men carrying the –174C allele had a relative risk of coronary heart disease of 1·54 (95% CI 1·0–2·23, P=0·048) and this effect was greatest in smokers (compared to GG non-smokers, RR 2·66, CI 1·64–4·32). These effects remained statistically significant after adjusting for classical risk factors including blood pressure (P=0·04). The –572C allele (frequency 0·05, 0·04–0·06) was not associated with a significant effect on blood pressure, fibrinogen or relative risk of coronary heart disease. In a subset of the genotyped men (n=494), carriers of the –174C allele had higher levels of C-reactive protein than non-carriers.
Conclusions These data confirm the importance of the inflammatory system in the development of coronary heart disease. They suggest that, at least in part, the effect of the IL-6 –174G>C polymorphism on blood pressure is likely to be operating through inflammatory mechanisms, but the genotype effect on coronary heart disease risk is largely unexplained by its effect on blood pressure. The molecular mechanisms whereby genetically determined differences in plasma levels of IL-6 are having these effects remain to be determined.
Key Words: Interleukin-6, polymorphisms, systolic blood pressure, inflammation, prospective study, smoking
f1 Correspondence: Professor Steve Humphries, Division of Cardiovascular Genetics, Department of Medicine, UCL Medical School, Rayne Institute, University Street, London WC1E 6JJ, U.K.
References
- Keller ET, Wanagat J, Ershler WB. Molecular and cellular biology of interleukin-6 and its receptor. Frontiers in Bioscience. 1996;1:340–357
- Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265:621–636[ISI][Medline]
- Ridker PM, Hennekens CH, Buring JE, Sc D, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–843
[Abstract/Free Full Text] - Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 1999;19:972–978
[Abstract/Free Full Text] - Mohamed-Ali V, Goodrick S, Rawesh A. Human subcutaneous adipose tissue releases IL-6 but not TNF-a in vivo. J Clin Endo Metab. 1997;82:4196–4200
[Abstract/Free Full Text] - Stephens JM, Butts MD, Pekala PH. Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by tumor necrosis factor-alpha. J Mol Endocrinol. 1992;9:61–72[Abstract]
- Reed MJ, Topping L, Coldham NG, Purohit A, Ghilchik MW, James VH. Control of aromatase activity in breast cancer cells: the role of cytokines and growth factors. J Steroid Biochem Mol Biol. 1993;44:589–596[CrossRef][ISI][Medline]
- Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767–1772
[Abstract/Free Full Text] - Biasucci LM, Vitelli A, Liuzzo G. Elevated levels of interleukin-6 in unstable angina. Circulation. 1996;94:874–877
[Abstract/Free Full Text] - Fishman D, Faulds G, Jeffery R. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102:1369–1376[ISI][Medline]
- Lancet. 1988;352:1649–1655[CrossRef]
- Jones KG, Brull DJ, Brown LC. Interleukin-6, (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation. 2001;103:2260–2265
[Abstract/Free Full Text] - Miller GJ, Bauer KA, Barzegar S. Increased activation of the haemostaic system in men at high risk of fatal coronary heart disease. Thromb Haemost. 1996;75:767–771[ISI][Medline]
- Seed M, Humphries SE, Ayres KL, Miller GJ. Lipoprotein (a) as a predictor for myocardial infarction in the Second Northwick Park Heart Study—a prospective study in middle-aged men. Am J Med. 2001;110:22–27[CrossRef][ISI][Medline]
- Medical Research Council's Committee on Chronic Bronchitis, Questionnaire on Respiratory Symptoms, 1995
- Prineas, RJ, Crow, RS, Blackburn, H, The Minnesota Code Manual of Electrocardiographic Findings, 1982
- Public Health Eur. 1976;5:157–164
- Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215
[Free Full Text] - Day IN, Humphries SE, Richards S. High-throughput genotyping using horizontal polyacrylamide gels with wells arranged for microplate array diagonal gel electrophoresis (MADGE). Biotechniques. 1995;19:830–835[ISI][Medline]
- Terry CF, Loukaci V, Green FR. Co-operative influence of genetic polymorphisms on interleukin-6 transcriptional regulation. J Biol Chem. 2000;275:18138–18144
[Abstract/Free Full Text] - Kannel WB. Fifty years of Framingham Study contributions to understanding hypertension. J Hum Hypertens. 2000;14:83–90[CrossRef][ISI][Medline]
- Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissue of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83:847–850
[Abstract/Free Full Text] - Akira S, Nishio Y, Tanaka T. Transcription factors NF Il-6 and APRF involved in gp130-mediated signalling pathway. Ann NY Acad Sci. 1995;762:15–27[Medline]
- Pottratz ST, Bellido T, Mocharla H, Crabb D, Manolagas SC. 17 Beta Estradiol inhibits expression of human interleukin-6 promoter-reporter constructs by a receptor-dependent mechanism. J Clin Invest. 1994;93:944–950[ISI][Medline]
- Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L. Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998;334:297–314[ISI][Medline]
- Lowe GDO, Rumley A. Coagulation, fibrinolysis and cardiovascular disease. Fibrinolysis & Proteolysis. 1999;13:91–98[CrossRef]
- Woodward M, Rumley A, Tunstall-Pedoe H, Lowe GDO. Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematology. 1999;104:246–257[CrossRef][ISI][Medline]
- Takano M, Itoh N, Yayama K, Yamano M, Ohtani R, Okamoto H. Interleukin-6 as a mediator responsible for inflammation-induced increase in plasma angiotensinogen. Biochem Pharmacol. 2000;45:201–206
- Soden M, Klett C, Hasmann T, Hackenthal E. Angiotensinogen: an acute-phase protein? Hypertension. 1994;23:126–130
- Schorr U, Blaschke K, Turan S, Distler A, Sharma AM. Relationship between angiotensinogen, leptin and blood pressure levels in young normotensive men. J Hyperten. 1998;16:1475–1480[CrossRef][ISI][Medline]
- Gharavi AG, Lipkowitz ML, Diamond JA, Chamie R, Phillips RA. Ambulatory blood pressure monitoring for detecting the relation between angiotensinogen gene polymorphism and hypertension. Am J Hypertens. 1997;10:687–691[CrossRef][ISI][Medline]
- Winklemann BR, Russ AP, Nauck M. Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. Am Heart J. 1999;137:698–705[CrossRef][ISI][Medline]
- Bigda J, Narkiewicz K, Chrostowska M. No effect of genetic variation at the angiotensinogen locus on ambulatory blood pressure level in normotensive subjects. Am J Hypertens. 1997;10:692–695[CrossRef][ISI][Medline]
- Niu T, Chen C, Yang J. Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene. Ann Epidemiol. 1999;9:245–253[CrossRef][ISI][Medline]
- Greenwel P, Iraburu MJ, Reyes-Romero M. Induction of an acute phase response in rats stimulates the expression of alpha l(I) procollagen messenger ribonucleic acid in their livers. Possible role of interleukin-6. Lab Invest. 1995;72:83–91[ISI][Medline]
- Duncan MR, Berman B. Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6. J Invest Dermatol. 1991;97:686–692[ISI][Medline]
- Silacci P, Dayer J, Desgeorges A, Peter R, Manueddu C, Guerne P. Interleukin (IL)-6 and its soluble receptor induce TIMP-1 expression in synoviocytes and chondrocytes, and block IL-1-induced collagenolytic activity. Biol Chem. 1998;273:13625–13629
- Roeb E, Graeve L, Mullberg J, Matern S, Rose-John S. TIMP-1 protein expression is stimulated by IL-1 beta and IL-6 in primary rat hepatocytes. Ann NY Acad Sci. 1995;762:462–464[Medline]
- Rus HG, Vlaicu R, Niculescu F. Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis. 1996;127:263–271[CrossRef][ISI][Medline]
- Sukovich DA, Kauser K, Shirley FD, DelVecchio V, Halks-Miller M, Rubanyi GM. Expression of interleukin-6 in atherosclerotic lesions of male ApoE-knockout mice: inhibition by 17beta-estradiol. Arterioscler Thromb Vasc Biol. 1998;18:1498–1505
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Shen, D. K. Arnett, P. Perez-Martinez, L. D. Parnell, C.-Q. Lai, J. M. Peacock, J. E. Hixson, M. Y. Tsai, R. J. Straka, P. N. Hopkins, et al. The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN study,boxs J. Lipid Res., August 1, 2008; 49(8): 1839 - 1845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Trichopoulou, N. Yiannakouris, C. Bamia, V. Benetou, D. Trichopoulos, and J. M. Ordovas Genetic Predisposition, Nongenetic Risk Factors, and Coronary Infarct Arch Intern Med, April 28, 2008; 168(8): 891 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Liao, J.-T. Lin, C.-Y. Wu, S.-P. Huang, M.-T. Lin, A. S.-H. Wu, Y.-J. Huang, and M.-S. Wu Serum Interleukin-6 Level but not Genotype Predicts Survival after Resection in Stages II and III Gastric Carcinoma Clin. Cancer Res., January 15, 2008; 14(2): 428 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M H A Malik, F Jury, A Bayat, W E R Ollier, and P R Kay Genetic susceptibility to total hip arthroplasty failure: a preliminary study on the influence of matrix metalloproteinase 1, interleukin 6 polymorphisms and vitamin D receptor Ann Rheum Dis, August 1, 2007; 66(8): 1116 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Humphries, J. A. Cooper, P. J. Talmud, and G. J. Miller Candidate Gene Genotypes, Along with Conventional Risk Factor Assessment, Improve Estimation of Coronary Heart Disease Risk in Healthy UK Men Clin. Chem., January 1, 2007; 53(1): 8 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Shaw Genetics of postoperative complications following thoracic surgery. Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 327 - 345. [Abstract] [PDF]
|
|
|
|
 |
|
 L Morgan, J Cooper, H Montgomery, N Kitchen, and S E Humphries The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to cerebral aneurysms J. Neurol. Neurosurg. Psychiatry, August 1, 2006; 77(8): 915 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yamada, N. Metoki, H. Yoshida, K. Satoh, S. Ichihara, K. Kato, T. Kameyama, K. Yokoi, H. Matsuo, T. Segawa, et al. Genetic Risk for Ischemic and Hemorrhagic Stroke Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1920 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. C. de Geus Genetic pleiotropy in depression and coronary artery disease. Psychosom Med, March 1, 2006; 68(2): 185 - 186. [Full Text] [PDF]
|
|
|
|
|
|
J. M. McCaffery, N. Frasure-Smith, M.-P. Dube, P. Theroux, G. A. Rouleau, Q. Duan, and F. Lesperance Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin. Psychosom Med, March 1, 2006; 68(2): 187 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, Y. Berthier-Schaad, M. D. Fallin, N. E. Fink, R. P. Tracy, M. J. Klag, M. W. Smith, and J. Coresh IL-6 Haplotypes, Inflammation, and Risk for Cardiovascular Disease in a Multiethnic Dialysis Cohort J. Am. Soc. Nephrol., March 1, 2006; 17(3): 863 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P.S. Sie, F. A. Sayed-Tabatabaei, H.-H. S. Oei, A. G. Uitterlinden, H. A.P. Pols, A. Hofman, C. M. van Duijn, and J. C.M. Witteman Interleukin 6 -174 G/C Promoter Polymorphism and Risk of Coronary Heart Disease: Results from the Rotterdam Study and a Meta-Analysis Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 212 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Bruunsgaard Physical activity and modulation of systemic low-level inflammation J. Leukoc. Biol., October 1, 2005; 78(4): 819 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Leibovici, H. B. Grossman, C. P. Dinney, R. E. Millikan, S. Lerner, Y. Wang, J. Gu, Q. Dong, and X. Wu Polymorphisms in Inflammation Genes and Bladder Cancer: From Initiation to Recurrence, Progression, and Survival J. Clin. Oncol., August 20, 2005; 23(24): 5746 - 5756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Shaw, A. A. Vaporciyan, X. Wu, T. M. King, M. R. Spitz, J. B. Putnam, and B. F. Dickey Inflammatory Gene Polymorphisms Influence Risk of Postoperative Morbidity After Lung Resection Ann. Thorac. Surg., May 1, 2005; 79(5): 1704 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Weger, I. Steinbrugger, A. Haas, W. Marz, Y. El-Shabrawi, W. Weger, O. Schmut, and W. Renner Role of the Interleukin-6 -174 G>C Gene Polymorphism in Retinal Artery Occlusion Stroke, February 1, 2005; 36(2): 249 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Huber, C. Grimm, S. Jirecek, R. Zeillinger, K. Heim, P. Husslein, and L. Hefler An lnterleukin-6 Gene Promoter Polymorphism and Unexplained Late Intrauterine Fetal Death: A Multicenter Study Reproductive Sciences, January 1, 2005; 12(1): 33 - 36. [Abstract] [PDF]
|
|
|
|
|
|
M. Bennermo, C. Held, S. Stemme, C.-G. Ericsson, A. Silveira, F. Green, and P. Tornvall Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases? Clin. Chem., November 1, 2004; 50(11): 2136 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Freeman, F. McManus, E. A. Brown, L. Cherry, J. Norrie, J. E. Ramsay, P. Clark, I. D. Walker, N. Sattar, and I. A. Greer Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia Hypertension, November 1, 2004; 44(5): 708 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Kunicki, A. B. Federici, D. R. Salomon, J. A. Koziol, S. R. Head, T. S. Mondala, J. D. Chismar, L. Baronciani, M. T. Canciani, and I. R. Peake An association of candidate gene haplotypes and bleeding severity in von Willebrand disease (VWD) type 1 pedigrees Blood, October 15, 2004; 104(8): 2359 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Harding, S. Dhamrait, A. Whitelaw, S. E. Humphries, N. Marlow, and H. E. Montgomery Does Interleukin-6 Genotype Influence Cerebral Injury or Developmental Progress After Preterm Birth? Pediatrics, October 1, 2004; 114(4): 941 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J J McCarthy, A Parker, R Salem, D J Moliterno, Q Wang, E F Plow, S Rao, G Shen, W J Rogers, L K Newby, et al. Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes J. Med. Genet., May 1, 2004; 41(5): 334 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Humphries, P. M. Ridker, and P. J. Talmud Genetic Testing for Cardiovascular Disease Susceptibility: A Useful Clinical Management Tool or Possible Misinformation? Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 628 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. DeMichele, A.-M. Martin, R. Mick, P. Gor, L. Wray, M. Klein-Cabral, G. Athanasiadis, T. Colligan, E. Stadtmauer, and B. Weber Interleukin-6 -174G->C Polymorphism Is Associated with Improved Outcome in High-Risk Breast Cancer Cancer Res., November 15, 2003; 63(22): 8051 - 8056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Harding, S. Dhamrait, A. Millar, S. Humphries, N. Marlow, A. Whitelaw, and H. Montgomery Is Interleukin-6 -174 Genotype Associated With the Development of Septicemia in Preterm Infants? Pediatrics, October 1, 2003; 112(4): 800 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M.L. Chapman, J. P. Beilby, S. E. Humphries, L. J. Palmer, P. L. Thompson, and J. Hung Association of an allelic variant of interleukin-6 with subclinical carotid atherosclerosis in an Australian community population Eur. Heart J., August 2, 2003; 24(16): 1494 - 1499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Landi, V. Moreno, L. Gioia-Patricola, E. Guino, M. Navarro, J. de Oca, G. Capella, and F. Canzian Association of Common Polymorphisms in Inflammatory Genes Interleukin (IL)6, IL8, Tumor Necrosis Factor {alpha}, NFKB1, and Peroxisome Proliferator-activated Receptor {gamma} with Colorectal Cancer , Cancer Res., July 1, 2003; 63(13): 3560 - 3566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Hefler, C. Grimm, S. Ackermann, S. Malur, A. R. Radjabi-Rahat, S. Leodolter, M. W. Beckmann, R. Zeillinger, H. Koelbl, and C. B. Tempfer An Interleukin-6 Gene Promoter Polymorphism Influences the Biological Phenotype of Ovarian Cancer Cancer Res., June 15, 2003; 63(12): 3066 - 3068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Fernandez-Real and W. Ricart Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome Endocr. Rev., June 1, 2003; 24(3): 278 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. L. Biondi-Zoccai, A. Abbate, G. Liuzzo, and L. M. Biasucci Atherothrombosis, inflammation, and diabetes J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pola, A. Flex, E. Gaetani, R. Flore, M. Serricchio, and P. Pola Synergistic Effect of -174 G/C Polymorphism of the Interleukin-6 Gene Promoter and 469 E/K Polymorphism of the Intercellular Adhesion Molecule-1 Gene in Italian Patients With History of Ischemic Stroke Stroke, April 1, 2003; 34(4): 881 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jerrard-Dunne, M. Sitzer, P. Risley, D. A. Steckel, A. Buehler, S. von Kegler, and H. S. Markus Interleukin-6 Promoter Polymorphism Modulates the Effects of Heavy Alcohol Consumption on Early Carotid Artery Atherosclerosis: The Carotid Atherosclerosis Progression Study (CAPS) Stroke, February 1, 2003; 34(2): 402 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.H. Gomma, M.A. Elrayess, C.J. Knight, E. Hawe, K.M. Fox, and S.E. Humphries The endothelial nitric oxide synthase (Glu298Asp and -786T>C) gene polymorphisms are associated with coronary in-stent restenosis Eur. Heart J., December 2, 2002; 23(24): 1955 - 1962. [Abstract] [PDF]
|
|
|
|
|
|
N. S. Jenny, R. P. Tracy, M. S. Ogg, L. A. Luong, L. H. Kuller, A. M. Arnold, A. R. Sharrett, and S. E. Humphries In the Elderly, Interleukin-6 Plasma Levels and the -174G>C Polymorphism Are Associated With the Development of Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2066 - 2071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Athan, J. H. Lee, A. Arriaga, R. P. Mayeux, and B. Tycko Polymorphisms in the Promoter of the Human APP Gene: Functional Evaluation and Allele Frequencies in Alzheimer Disease Arch Neurol, November 1, 2002; 59(11): 1793 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Papafili, M. R. Hill, D. J. Brull, R. J. McAnulty, R. P. Marshall, S. E. Humphries, and G. J. Laurent Common Promoter Variant in Cyclooxygenase-2 Represses Gene Expression: Evidence of Role in Acute-Phase Inflammatory Response Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1631 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Mitchison and J. Roes Patterned variation in murine MHC promoters PNAS, August 6, 2002; 99(16): 10561 - 10566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Basso, G. D.O. Lowe, A. Rumley, A. D. McMahon, and S. E. Humphries Interleukin-6 -174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS) Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 599 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lamblin, C. Bauters, and N. Helbecque Gene polymorphisms of pro- (or anti-) inflammatory cytokines and vascular disease Eur. Heart J., December 2, 2001; 22(24): 2219 - 2220. [PDF]
|
|
|
|
|
|
F. Basso, G. D.O. Lowe, A. Rumley, A. D. McMahon, and S. E. Humphries Interleukin-6 -174G>C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS) Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 599 - 604. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||