Association between genetic variations of the transforming growth factor ß receptor type III and asthma in a Korean population.
Transforming growth factor-beta (TGF-ß) and its receptors have been suggested to play key roles in the pathogenesis of asthma. The aim of this study was to evaluate the effects of genetic variations in the TGF-ß receptor type III (TGFBR3) on asthma and on its related phenotypes in the general population. A cohort of 2,118 subjects aged from 10 to 18 years responded to a questionnaire concerning asthma symptoms and risk factors. Methacholine airway hyperresponsiveness (AHR), skin test responses to common aeroallergens, and serum total IgE levels were evaluated in the cohort. A total of 19 SNPs for TGFBR3 were found using direct re-sequencing in 24 healthy adults. Of these, informative SNPs [+44T>C (S15F) and +2753G>A at 3'UTR] were selected and scored using the high throughput single base extension method. Atopy was identified in subjects with 44T>C allele [P=0.04, OR (95% CI)=0.79 (0.62-0.99)] and in subjects with Ht1 (CG) more frequently than in subjects with other haplotypes [P=0.04, OR (95% CI)=1.27 (1.01-1.59)]. The A allele in 2753G>A was more common in subjects with non-atopic asthma [OR (95% CI)=1.76 (1.01-3.05)]. A significant association was found between non-atopic asthma and 44T_2753A [OR (95% CI) =2.16 (1.22-3.82)]. Genetic variations in TGFBR3 appear to be associated with a genetic predisposition to development of asthma and to phenotypes of asthma. Also, the minor allele 2753G and the haplotype TA in the TGFBR3 gene were associated with a pathogenesis of non-atopic asthma.
Kim
Hee-Kyoo
HK
Department of Internal Medicine, Kosin University College of Medicine, Busan 602-702, Korea. naum67@naver.com
Jang
Tae-Won
TW
Jung
Mann-Hong
MH
Park
Heung-Woo
HW
Lee
Jong-Eun
JE
Shin
Eun-Soon
ES
Cho
Sang-Heon
SH
Min
Kyung-Up
KU
Kim
You-Young
YY
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D015810:Linkage Disequilibrium; D008297:Male; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D007073:Immunoglobulin E
Pulm Pharmacol Ther. 2003;16(4):181-96
12850120
Eur Respir J. 2000 Feb;15(2):248-53
10706487
Curr Opin Immunol. 2004 Dec;16(6):709-16
15511662
J Immunol. 1986 Apr 1;136(7):2348-57
2419430
Clin Exp Allergy. 2001 Apr;31(4):582-9
11359426
Ann Allergy Asthma Immunol. 2003 Nov;91(5):472-6
14692431
Clin Exp Allergy. 2002 Sep;32(9):1305-9
12220468
Am J Respir Cell Mol Biol. 2002 Feb;26(2):202-8
11804871
Methods Mol Med. 2005;117:69-80
16118446
Biochem Biophys Res Commun. 1992 Nov 30;189(1):356-62
1333192
Nature. 1992 Oct 22;359(6397):693-9
1436033
Science. 1998 Dec 18;282(5397):2258-61
9856949
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):124-30
14734460
Exp Mol Med. 2008 Aug 31;40(4):461-76
18779659
J Allergy Clin Immunol. 2005 Mar;115(3):527-33
15753900
Genome Res. 1999 Aug;9(8):720-31
10447507
J Allergy Clin Immunol. 1999 Aug;104(2 Pt 1):311-6
10452750
Science. 1996 Sep 13;273(5281):1516-7
8801636
J Allergy Clin Immunol. 2006 Jan;117(1):92-6
16387590
Clin Rev Allergy Immunol. 2003 Feb;24(1):85-110
12644720
Eur Respir J. 2000 Aug;16(2):349-54
10968513
Mol Biotechnol. 2002 Oct;22(2):179-89
12405265
Eur J Immunol. 2005 Jan;35(1):198-206
15593298
J Biol Chem. 1995 Jun 2;270(22):13567-72
7768960
Trends Biochem Sci. 2004 May;29(5):265-73
15130563
Curr Dir Autoimmun. 2002;5:62-91
11826761
J Allergy Clin Immunol. 1999 Nov;104(5):895-901
10550729
J Exp Med. 2001 Sep 17;194(6):809-21
11560996
Immunol Lett. 2002 Jun 3;82(1-2):85-91
12008039
J Biol Chem. 2001 Oct 26;276(43):39608-17
11546783