Go to the content. | Move to the navigation | Go to the site search | Go to the menu | Contacts | Accessibility

| Create Account

Tikhonoff, Valerie (2008) Blood pressure and metabolic phenotypes in relation to SAH gene variants and ADRB1 Arg389Gly and ADRAB2 I/D polymorphisms in white family-based population samples. [Ph.D. thesis]

Full text disponibile come:

[img]
Preview
Documento PDF
410Kb

Abstract (english)

Objectives: Aim of the present doctoral dissertation is independent confirmation in family-based population samples, using strict appropriate statistical approach, of the associations, if any, between blood pressure (BP) and related metabolic phenotypes, analysed as continuous traits, and variations in candidate genes arising from experimental animal models [Spontaneously hypertensive rat-clone A-Hypertension-associated (SAH) gene], and from physiological cascades of the adrenergic system [alfa2B- (ADRAB2) and beta1- (ADRB1) adrenergic receptors].
Methods and Results: The SAH gene variants were evaluated in the frame of the European Project On Genes in Hypertension. In details, 2603 relatives from 560 families and 31 unrelated subjects (mean age 38.8?15.7 years; 52.1% women) were randomly recruited from six European populations. Systolic/diastolic BP, body mass index, triceps skinfold, waist-to-hip ratio, serum total and HDL cholesterol, serum triglycerides and blood glucose were measured. All subjects were genotyped for the G-1606A and -962 del/ins polymorphisms and the allele frequencies were 11.8% and 29.5% for -1606A and -962del, respectively. Lewontin’s D’ was 0.97 (p<0.0001). Haplotype frequencies were 58.8% for -1606G plus -962ins, 29.5% for -1606G plus -962del, and 11.7% for -1606A plus -962ins. Both before and after adjustment for covariates, none of the phenotype-genotype associations approached statistical significance. Family-based analyses did not reveal any population stratification (P?0.67) as a possible explanation of those negative results.
The association studies between ADRB1 Arg389Gly and ADRA2B I/D polymorphisms of the beta1- and alfa2B-adrenergic receptors with BP and metabolic phenotypes, were conducted in a subsample of the EPOGH cohort. 1802 relatives from 175 families and 79 unrelated subjects (mean age 45.5?15.7 years; 51.1% women) were randomly recruited from a Caucasian population living in Northern Belgium. Systolic/diastolic BP, body mass index, waist-to-hip ratio, serum total and HDL cholesterol were measured. All subjects were genotyped for the ADRA2B I/D and ADRB1 Arg389Gly polymorphisms. The ADRA2B genotypes (II 45.7%, ID 41.7%, and DD 12.5%; P=0.05) and the ADRB1 genotypes (ArgArg 56.2%, ArgGly 36.9%, and GlyGly 6.9%; P=0.66) did not deviate from Hardy–Weinberg proportions. ADRB1 ArgArg homozygotes, compared with Gly allele carriers, had higher diastolic BP (79.4 vs 78.4 mmHg; P=0.012), and higher serum HDL cholesterol (1.33 vs 1.29 mmol/l; P=0.020). None of the other cardiovascular or metabolic phenotypes in relation to the two polymorphisms reached significance. The family-based analyses did not reveal population stratification (P?0.23).
Conclusions: The present study gives evidence in favour of association of diastolic BP and HDL cholesterol with the ADRB1 Arg389Gly polymorphism in the absence of population stratification. However, the evidences supporting association of hypertension or hypertension-related phenotypes with the SAH gene remain equivocal in human studies.


Statistiche Download - Aggiungi a RefWorks
EPrint type:Ph.D. thesis
Tutor:Casiglia, Edoardo
Ph.D. course:Ciclo 20 > Corsi per il 20simo ciclo > IPERTENSIONE ARTERIOSA E BIOLOGIA VASCOLARE
Data di deposito della tesi:13 March 2008
Anno di Pubblicazione:13 March 2008
Key Words:Hypertension, Metabolic phenotype, polymorphism, population, SAH gene, adrenoreceptor
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/09 Medicina interna
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Medicina Clinica e Sperimentale
Codice ID:1021
Depositato il:25 Nov 2008
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1. Snieder H, Harshfield GA, Treiber FA. Heritability of blood pressure and hemodynamics in African- and European-American youth. Hypertension 2003; 41:1196–1201. Cerca con Google

2. Ward R. Familial aggregation and genetic epidemiology of blood pressure. In Laragh, J.H. and Brenner, B.M. (eds), Hypertension: Pathophysiology, Diagnosis and Management 1990. Raven Press, New York, 81–100. Cerca con Google

3. Feinleib M, Garrison RJ, Fabsitz R, Christian JC, Hrubec Z, Borhani NO, Kannel WB, Rosenman R, Schwartz JT, Wagner JO. The NHLBI twin study of cardiovascular disease risk factors: methodology and summary of results. Am J Epidemiol 1977; 106: 284–285 Cerca con Google

4. Longini IM, Higgins MW, Hinton PC, Moll PC, Keller JB. Environmental and genetic sources of familial aggregation of blood pressure in Tecumseh. Michigan. Am J Epidemiol 1984; 120:131–144. Cerca con Google

5. Rice T, Vogler GP, Perusse L, Bouchard C, Rao DC. Cardiovascular risk factors in a French Canadian population: resolution of genetic and familial environmental effects on blood pressure using twins, adoptees, and extensive information on environmental correlates. Genet Epidemiol 1989; 6: 571–588 Cerca con Google

6. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell 2001; 104:545–556. Cerca con Google

7. Harrap SB. Where are all the blood-pressure genes? Lancet 2003;361:2149–2151. Cerca con Google

8. Mein CA, Caulfield MJ, Dobson RJ, Munroe PB. Genetic of essential hypertension. Hum Mol Genet 2004; 13:R169–R175. Cerca con Google

9. Binder A. A review of the genetics of essential hypertension. Curr Opin Cardiol 2007; 22:176-184. Cerca con Google

10. Gong M, Hubner N. Molecular genetics of human hypertension. Clin Sci 2006; 110:315-326. Cerca con Google

11. Spielman RS, Ewens WJ. The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 1996; 59: 983–989. Cerca con Google

12. Stoll M, Kwitek-Black AE, Cowley AW Jr, Harris EL, Harrap SB, Krieger JE, Printz MP, Provoost AP, Sassard J, Jacob HJ. New target regions for human hypertension via comparative genomics.Genome Res 2000; 10:473-82. Cerca con Google

13. Rapp JP. Genetic analysis of inherited hypertension in the rat. Physiol Rev 2000; 80:135–172. Cerca con Google

14. Takahashi N, Smithies O. Gene targeting approaches to analyzing hypertension. J Am Soc Nephrol 1999; 17:1598–1605. Cerca con Google

15. Comuzzie AG, Allison DB. The search for human obesity genes. Science 1998; 280:1374–1377. Cerca con Google

16. Guo SW, Lange K. Genetic mapping of complex traits: promises, problems, and prospects. Theor Popul Biol 2000; 57:1–11. Cerca con Google

17. Altmuller J, Palmer LJ, Fischer G, Scherb H, Wjst M. Genomewide scans of complex human diseases: true linkage is hard to find. Am J Hum Genet 2001; 69:936–950. Cerca con Google

18. Iwai N, Inagami T. Isolation of preferentially expressed genes in the kidneys of hypertensive rats. Hypertension 1991; 17:161-169. Cerca con Google

19. Patel HR, Thiara AS, West KP, Lodwick D, Samani NJ. Increased expression of the SA gene in the kidney of the spontaneously hypertensive rat is localized to the proximal tubule. J Hypertens 1994; 12:1347-1352. Cerca con Google

20. Yang T, Hassan SA, Singh I, Smart A, Brosius FC, Holzman LB, Schnermann JB, Briggs JP. SA gene expression in the proximal tubule of normotensive and hypertensive rats. Hypertension 1996; 27:541-551. Cerca con Google

21. Samani NJ, Whitmore SA, Kaiser MA, Harris J, See CG, Callen DF, Lodwick D. Chromosomal assignment of the human SA gene to 16p13.11 and demonstration of its expression in the kidney. Biochem Biophys Res Commun 1994; 199:862-868. Cerca con Google

22. Iwai N, Katsuya T, Mannami T, Higaki J, Ogihara T, Kokame K, Ogata J, Baba S. Association between SAH, an acyl-CoA synthetase gene, and hypertriglyceridemia, obesity, and hypertension. Circulation 2002; 105:41-47. Cerca con Google

23. Fujino T, Kang MJ, Suzuki H, Iijima H, Yamamoto T. Molecular characterization and expression of rat acyl-CoA synthetase 3. J Biol Chem 1996; 271:16748-16752. Cerca con Google

24. Iwai N, Mannami T, Tomoike H, Ono K, Iwanaga Y. An acyl-CoA synthetase gene family in chromosome 16p12 may contribute to multiple risk factors. Hypertension 2003; 41:1041-1046. Cerca con Google

25. Telgmann R, Brand E, Nicaud V, Hagedorn C, Beining K, Schönfelder J, et al. SAH gene variants are associated with obesity-related hypertension in Caucasians: the PEGASE Study. J Hypertens 2007; 25:557-564. Cerca con Google

26. Haketa A, Soma M, Nakayama T, Sato M, Kosuge K, Aoi N, Matsumoto K. Two medium-chain acyl-coenzyme A synthetase genes, SAH and MACS1, are associated with plasma high-density lipoprotein cholesterol levels, but they are not associated with essential hypertension. J Hypertens 2004; 22:1903-1907. Cerca con Google

27. Benjafield AV, Iwai N, Ishikawa K, Wang WYS, Morris BJ. Overweight, But Not Hypertension, Is Associated with SAH Polymorphisms in Caucasians with Essential Hypertension. Hypertens Res 2003; 26:591-595. Cerca con Google

28. Kuznetsova T, Staessen J.A., Kawecka-Jaszcz K., Babeanu S., Caviglia E, Filipovsky J, Nachev C, Nikitin Y, Peleska. J and O’Brieni E. Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension. Blood Press Monit 2002; 7:215-224. Cerca con Google

29. Staessen J, O'Brien E, Atkins N, Bulpitt CJ, Cox J, Fagard R, O'Malley K, Thijs L, Amery A. The increase in blood pressure with age and body mass index is overestimated by conventional sphygmomanometry. Am J Epidemiol 1992; 136:450-9. Cerca con Google

30. 41st World Medical Assembly 1990 Declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. Bull Pan Am Health Organ 1990; 24:606-609. Cerca con Google

31. Petrie JC, O’Brien ET, Littler WA, de Swiet M. Recommendations on blood pressure measurement by a working party of the British Hypertension Society. BMJ 1989; 293:611-615. Cerca con Google

32. Staessen JA, Fagard R, Amery A. Life style as a determinant of blood pressure in the general population. Am J Hypertens 1994; 7:685-694. Cerca con Google

33. Abecasis G. R., Cardon L. R., and Cookson W. O. A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000; 66:279-292. Cerca con Google

34. Lindpaintner K, Hilbert P, Ganten D, Nadal-Ginard B, Inagami T, Iwai N. Molecular genetics of the SA-gene: cosegregation with hypertension and mapping to rat chromosome 1. J Hypertens 1993; 11:19-23. Cerca con Google

35. Iwai N, Tsujita Y, Kinoshita M. Isolation of a chromosome 1 region that contributes to high blood pressure and salt sensitivity. Hypertension 1998; 32:636-638. Cerca con Google

36. Iwai N, Inagami T. Identification of a candidate gene responsible for the high blood pressure of spontaneously hypertensive rats. J Hypertens 1992; 10:1155-1157. Cerca con Google

37. Harris EL, Dene H, Rapp JP. SA gene and blood pressure cosegregation using Dahl salt-sensitive rats. Am J Hypertens 1993; 6:330-334. Cerca con Google

38. Frantz SA, Kaiser M, Gardiner SM, Gauguier D, Vincent M, Thompson JR, Bennett T, Samani NJ. Successful isolation of a rat chromosome 1 blood pressure quantitative trait locus in reciprocal congenic strains. Hypertension 1998; 32:639-646. Cerca con Google

39. Cui ZH, Nemoto K, Kawakami K, Gonda T, Nabika T, Masuda J. Fine linkage mapping of the blood pressure quantitative trait locus region on rat chromosome 1. Hypertens Res 2002; 25:605-608. Cerca con Google

40. Hübner N, Lee Y-A, Lindpaintner K, Ganten D, Kreutz R. Congenic substitution mapping excludes SA as a candidate gene locus for a blood pressure quantitative trait locus on rat chromosome 1. Hypertension 1999; 34:643-648. Cerca con Google

41. Frantz S, Clemitson JR, Bihoreau MT, Gauguier D, Samani NJ. Genetic dissection of region around the Sa gene on rat chromosome 1: evidence for multiple loci affecting blood pressure. Hypertension 2001; 38:216-221. Cerca con Google

42. Vessey DA, Kelley M. Purification and partial sequencing of the XL-I form of xenobiotic-metabolizing medium chain fatty acid: CoA ligase from bovine liver mitochondria, and its homology with the essential hypertension protein. Biochem Biophys Acta 1997; 1346:231-236. Cerca con Google

43. Iwai N, Ohmichi N, Hanai K, Nakamura Y, Kinoshita M. Human SA gene locus as a candidate locus for essential hypertension. Hypertension 1994; 23:375-380. Cerca con Google

44. Lodwick D, Norman RI, Feeney G, West KP, Samani NJ. Immunohistochemical localisation of SA protein [Abstract]. J Hypertens 1998; 16:S45. Cerca con Google

45. Lamon-Fava S, Wilson PW, Schaefer EJ. Impact of body mass index on coronary heart disease risk factors in men and women. The Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1996; 16:1509-1515. Cerca con Google

46. Brodde OE. ?-1 and ?-2 adrenoceptor polymorphisms: Functional importance, impact on cardiovascular diseases and drug responses. Pharmacol Ther 2008; 117:1-29. Cerca con Google

47. Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M, et al. Identification of a three-amino acid deletion in the ?2(B)-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects. J Clin Endocrinol Metab 1999; 84: 2429-2433. Cerca con Google

48. Small KM, Brown KM, Forbes SL, Liggett SB. Polymorphic Deletion of Three Intracellular Acidic Residues of the 2B-Adrenergic Receptor Decreases G Protein-coupled Receptor Kinase-mediated Phosphorylation and Desensitization. J Biol Chem 2001; 276: 4917-4922. Cerca con Google

49. Defoor J, Martens K, Zielinska D, Matthijs G, Van Nerum H, Schepers D et al. The CAREGENE study: polymorphisms of the beta1-adrenoceptor gene and aerobic power in coronary artery disease. Eur Heart J 2006; 27: 808-816. Cerca con Google

50. Zhang H, Li X, Huang J, Li Y, Thijs L, Wang Z, et al. Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population. J Hypertens 2005; 23:2201-2207. Cerca con Google

51. Siitonen N, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, et al. Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study. Diabetologia 2004; 47:1416-1424. Cerca con Google

52. Sivenius K, Lindi V, Niskanen L, Laakso M, Uusitupa M. et al. Effect of a three-amino acid deletion in the alpha2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects. Int J Obes Relat Metab Disord 2001; 25:1609-1614. Cerca con Google

53. Li Y, Zagato L, Kuznetsova T, Tripodi G, Zerbini G, Richart T, Thijs L. et al. Angiotensin-converting enzyme I/D and alpha-adducin Gly460Trp polymorphisms: from angiotensin-converting enzyme activity to cardiovascular outcome. Hypertension 2007; 49:1291-1297. Cerca con Google

54. Lafontan M, Berlan M. Fat cell adrenergic receptors and the control of white and brown fat cell function. J Lipid Res 1993; 34:1057-1091. Cerca con Google

55. Mason DA, Moore JD, Green SA, Liggett SB. A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor. J Biol Chem 1999; 274:12670-12674. Cerca con Google

56. Sofowora GG, Dishy V, Muszkat M, Xie HG, Kim RB, Harris PA, Prasad HC, Byrne DW, Nair UB, Wood AJ, Stein CM. A common beta1-adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade. Clin Pharmacol Ther 2003; 73:366-371. Cerca con Google

57. Sharma A, Jeunemaitre X. The future of genetic association studies in hypertension: improving the signal-to-noise ratio. J Hypertens 2000; 18:811–814. Cerca con Google

58. Campbell H, Rudan I. Interpretation of genetic association studies in complex disease. The Pharmacogenomics Journal 2002; 2:349-360. Cerca con Google

59. Ioannidis JP, Boffetta P, Little J, O'Brien TR, Uitterlinden AG, Vineis P, Balding DJ, Chokkalingam A, Dolan SM, Flanders WD, Higgins JP, McCarthy MI, McDermott DH, Page GP, Rebbeck TR, Seminara D, Khoury MJ. Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol 2008; 37:120-132. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record