A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: A study of 1428 individuals in 248 families

Journal of Medical Genetics

Volumn 42, Issue 6, 2005, Pages 474-478

  Gaukrodger, N ^b   Mayosi, B M ^c,e   Imrie, H ^b   Avery, P ^b   Baker, M ^b   Connell, J M C ^d   Watkins, H ^c   Farrall, M ^c   Keavney, Bernard ^a,b  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d UNIVERSITY OF GLASGOW   (United Kingdom)

^e UNIVERSITY OF CAPE TOWN   (South Africa)

Author keywords

[No Author keywords available]

Indexed keywords

LEPTIN;

ADULT; ALLELE; ARTERY INTIMA PROLIFERATION; ARTERY MEDIA; ARTICLE; ATHEROSCLEROSIS; AUTOCRINE EFFECT; BLOOD PRESSURE; BODY MASS; CAROTID ARTERY DISEASE; DNA POLYMORPHISM; FAMILY STUDY; FEMALE; GENE; GENE MUTATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; HETEROZYGOTE; HOMOZYGOTE; HUMAN; LEP GENE; MAJOR CLINICAL STUDY; MALE; OBESITY; PARACRINE SIGNALING; PRIORITY JOURNAL; PULSE PRESSURE; QUANTITATIVE TRAIT; UNITED KINGDOM; UNTRANSLATED REGION;

ATHEROSCLEROSIS; BLOOD PRESSURE; BODY MASS INDEX; FAMILY HEALTH; GENE FREQUENCY; GENES; GENOTYPE; HUMANS; LEPTIN; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; TUNICA INTIMA; TUNICA MEDIA;

EID: 20544455535     PISSN: 00222593     EISSN: None     Source Type: Journal    
DOI: 10.1136/jmg.2004.027631     Document Type: Article

References (36)

1. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohamed SN, Hurst JA, Cheatham KH, Earley AR, Barnett AH, Prins JB, O'Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387(6636):903-8.
2. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD. A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 1998;18(3):213-5.
3. Maffei M, Stoffel M, Barone M, Moon B, Dammerman M, Ravussin E, Bogardus C, Ludwig DS, Flier JS, Talley M, et al. Absence of mutations in the human OB gene in obese/diabetic subjects. Diabetes 1996;45(5):679-82.
4. Carlsson B, Lindell K, Gabrielsson B, Karlsson C, Bjarnason R, Westphal O, Karlsson U, Sjostrom L, Carlsson LM. Obese (ob) gene defects are rare in human obesity. Obes Res 1997;5(1):30-5.
5. Le Stunff C, Le Bihan C, Schork NJ, Bougneres P. A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabetes 2000;49(12):2196-200.
6. Li WD, Reed DR, Lee JH, Xu W, Kilker RL, Sodam BR, Price RA. Sequence variants in the 5′ flanking region of the leptin gene are associated with obesity in women. Ann Hum Genet 1999;63(Pt 3):227-34.
7. Mammes O, Betoulle D, Aubert R, Herbeth B, Siest G, Fumeron F. Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight. Ann Hum Genet 2000;64(Pt 5):391-4.
8. Jiang Y, Wilk JB, Borecki I, Williamson S, DeStefano AL, Xu G, Liu J, Ellison RC, Province M, Myers RH. Common variants in the 5′ region of the leptin gene are associated with body mass index in men from the National Heart, Lung, and Blood Institute Family Heart Study. Am J Hum Genet 2004;75(2):220-30.
9. Lifton RP, Hopkins PN, Williams RR, Hollenberg NK, Williams GH, Dluhy RG. Evidence for heritability of non-modulating essential hypertension. Hypertension 1989;13(6 Pt 2):884-9.
10. Blacher J, Asmar R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 1999;33(5):1111-7.
11. Taniwaki H, Kawagishi T, Emoto M, Shoji T, Kanda H, Maekawa K, Nishizawa Y, Morii H. Correlation between the intima-media thickness of the carotid artery and aortic pulse-wave velocity in patients with type 2 diabetes. Vessel wall properties in type 2 diabetes. Diabetes Care 1999;22(11):1851-7.
12. Asmar R, Rudnichi A, Blacher J, London GM, Safar ME. Pulse pressure and aortic pulse wave are markers of cardiovascular risk in hypertensive populations. Am J Hypertens 2001;14(2):91-7.
13. Meaume S, Rudnichi A, Lynch A, Bussy C, Sebban C, Benetos A, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old. J Hypertens 2001;19(5):871-7.
14. Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37(5):1236-41.
15. Lewingtan S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360(9349):1903-13.
16. van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DA, Witteman JC. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study. Circulation 2004;109(9):1089-94.
17. Keavney B, McKenzie CA, Connell JM, Julier C, Ratcliffe PJ, Sobel E, Lathrop M, Farrall M. Measured haplotype analysis of the angiotensin-I converting enzyme gene. Hum Mol Genet 1998;7(11):1745-51.
18. Mayosi BM, Keavney B, Kardos A, Davies CH, Ratcliffe PJ, Farrall M, Watkins H. Electrocardiographic measures of left ventricular hypertrophy show greater heritability than echocardiographic left ventricular mass. Eur Heart J 2002;23(24):1963-71.
19. Keavney B, Bird R, Caiazza A, Casadei B, Conway J. Measurement of blood pressure using the auscultatory and oscillometric methods in the same cuff deflation: validation and field trial of the A&D TM2421 monitor. J Hum Hypertens 2000;14(9):573-9.
20. Salonen JT, Korpela H, Salonen R, Nyyssonen K. Precision and reproducibility of ultrasonographic measurement of progression of common carotid artery atherosclerosis. Lancet 1993;341(8853):1158-9.
21. Blankenhorn DH, Selzer RH, Crawford DW, Barth JD, Liu CR, Liu CH, Mack WJ, Alaupovic P. Beneficial effects of colestipol-niacin therapy on the common carotid artery. Two- and four-year reduction of intima-media thickness measured by ultrasound. Circulation 1993;88(1):20-8.
22. Adams MR, Nakagomi A, Keech A, Robinson J, McCredie R, Bailey BP, Freedman SB, Celermajer DS. Carotid intima-media thickness is only weakly correlated with the extent and severity of coronary artery disease. Circulation 1995;92(8):2127-34.
23. O'Connell JR, Weeks DE. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998;63(1):259-66.
24. Abecasis GR, Cherny SS, Cookson WO, Cardon LR. Merlin - rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 2002;30(1):97-101.
25. Dawson E, Abecasis GR, Bumpstead S, Chen Y, Hunt S, Beare DM, Pabial J, Dibling T, Tinsley E, Kirby S, Carter D, Papaspyridonos M, Livingstone S, Ganske R, Lohmussaar E, Zernant J, Tonisson N, Remm M, Magi R, Puurand T, Vilo J, Kurg A, Rice K, Deloukas P, Mott R, Metspolu A, Bentley DR, Cardon LR, Dunham I. A first-generation linkage disequilibrium map of human chromosome 22. Nature 2002;418(6897):544-8.
26. Abecasis GR, Cardon LR, Cookson WO. A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000;66(1):279-92.
27. Hasstedt SJ. Variance components/major locus likelihood approximation for quantitative, polychotomous, and multivariate data. Genet Epidemiol 1993;10(3):145-58.
28. Thomas DC, Clayton DG. Betting odds and genetic associations. J Natl Cancer Inst 2004;96(6):421-3.
29. Misquitta CM, Iyer VR, Werstiuk ES, Grover AK. The role of 3′-untranslated region (3′-UTR) mediated mRNA stability in cardiovascular pathophysiology. Mol Cell Biochem 2001;224(1-2):53-67.
30. Huang JL, Gao PS, Mathias RA, Yao TC, Chen LC, Kuo ML, Hsu SC, Plunkett B, Togias A, Barnes KC, Stellato C, Beaty TH, Huang SK. Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability. Hum Mol Genet 2004;13(21):2691-7.
31. Schafer K, Halle M, Goeschen C, Dellas C, Pynn M, Loskutoff DJ, Konstantinides S. Leptin promotes vascular remodeling and neointimal growth in mice. Arterioscler Thromb Vasc Biol 2004;24(1):112-7.
32. Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA 2002;287(13):1706-9.
33. Karvonen MK, Pesonen U, Heinonen P, Laakso M, Rissanen A, Naukkarinen H, Valve R, Uusitupa MI, Koulu M. Identification of new sequence variants in the leptin gene. J Clin Endocrinol Metab 1998;83(9):3239-42.
34. Shintani M, Ikegami H, Fujisawa T, Kawaguchi Y, Ohishi M, Katsuya T, Higaki J, Shimamota K, Ogihara T. Leptin gene polymorphism is associated with hypertension independent of obesity. J Clin Endocrinol Metab 2002;87(6):2909-12.
35. Department of Health. Health Survey of England 2002. London: The Stationary Office, 2003.
36. Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science 2004;305(5685):869-72.