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|Title: ||Genetic analysis of eight candidate genes in South Asian and Caucasian rheumatoid arthritis patients of the East Midlands|
|Authors: ||Ghelani, Anant M.|
|Issue Date: ||2006|
|Publisher: ||© Anant Ghelani|
|Abstract: ||Rheumatoid Arthritis (RA) is a chronic musculoskeletal disease of unknown
aetiology. RA is a complex polygenic and multifactorial disease and has not been
analysed comprehensively among South Asians, specifically in the East Midlands.
Two genetic approaches were used; case-control and sib-TDT analyses. Ten
polymorphisms of eight genes (ACE, VDR, A2M, GSTTt and GSTMt, TNFRII,
FcyRIIIA and CRH) were analysed in South Asians (134 patients, 66 unaffected sibs,
149 random controls) and Caucasians (137 pateints, 83 unaffected sibs, 150 random
The epidemiological results suggest that the South Asians were progressing to the
disease significantly earlier (X2 = 21.01, 5 df, P < 0.005). The gender distribution
(male:female) was 1:4 in South Asians and 1:3 in Caucasians.
Significant genetic associations were observed with VDR Bsm I B-B genotype (OR=
2.08, Cl 1.23- 3.52, P < 0.05), A2M 2-2 genotype (OR= 3.99, Cl 1.19- 17.18, P <
0.05), and GST Tinull genotype (OR= 2.81, Cl 1.40- 5.77, P < 0.002) among South
Asian RAs. In Caucasians, TNFRII R-R (OR= 3.16, Cl 1.20-9.26, P < 0.05), A2M 1-
1 (OR= 2.09, Cl 1.21-3.64, P < 0.05) and GST Ttnull (OR= 1.97, Cl 1.07- 3.68, P <
0.05) genotypes were associated with RA. In the majority of cases, recessive and
multiplicative modes of inheritance explained the observed associations. There were
no confounding interactions between the genotypes showing significant associations
in both groups.
Overall this study demonstrates that ethnic and genetic variation plays a significant
role in RA susceptibility and progression. The observed genetic associations may
have pharmacogenetic and diagnostic implications. Mechanisms to some|
|Description: ||A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.|
|Appears in Collections:||PhD Theses (Sport, Exercise and Health Sciences)|
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