The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis

Jaakkola, E., Crane, A. M., Laiho, K., Herzberg, I., Sims, A. M., Bradbury, L., Calin, A., Brophy, S., Kauppi, M., Kaarela, K., Wordsworth, B. P., Tuomilehto, J., & Brown, M. A. (2004) The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis. Rheumatology, 43(1), pp. 32-38.

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To determine whether genetic polymorphisms in or near the transforming growth factor β1 (TGFB1) locus were associated d with susceptibility to or severity of ankylosing spondylitis (AS).


Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index).


A weak association was noted between the rare TGFB1 + 1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/ +915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. Conclusion. This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

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ID Code: 89543
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :21
Export Date: 21 September 2015
Correspondence Address: Brown, M.A.; Spondyloarthritis/Bone Dis. Res. Grp, Roosevelt Drive, Headington, Oxford OX3 7BN, United Kingdom
Keywords: Cytokines, Genetic aetiology, Microsatellites, Polygenic, Spondyloarthropathy, transforming growth factor beta1, adult, allele, ankylosing spondylitis, article, centromere, chromosome 19, controlled study, data analysis, disease activity, disease duration, disease predisposition, disease severity, family study, female, Finland, functional assessment, gene function, gene locus, genetic association, genetic code, genetic linkage, genetic parameters, genetic polymorphism, genotype, haplotype, human, major clinical study, male, microsatellite marker, onset age, parent, population research, priority journal, promoter region, quantitative trait, questionnaire, scoring system, single nucleotide polymorphism, statistical analysis, symptomatology, United Kingdom, Chi-Square Distribution, England, Genetic Predisposition to Disease, Haplotypes, HLA-B27 Antigen, Humans, Linkage Disequilibrium, Microsatellite Repeats, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Spondylitis, Ankylosing, Transforming Growth Factor beta
DOI: 10.1093/rheumatology/keg457
ISSN: 1462-0324
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright British Society for Rheumatology 2003
Deposited On: 27 Oct 2015 01:20
Last Modified: 27 Oct 2015 01:20

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