Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthritis in South Asians and Caucasians of East Midlands in the United Kingdom

Abstract

Genetic associations of TNFR2, VDR (Bsm I and Fok I), A2M, GSTT(1), GSTM(1) and ACE in South Asian and Caucasian patients with rheumatoid arthritis (RA) were assessed in this study. DNA samples from South Asians (134 cases, 149 controls) and Caucasians (137 cases, 150 controls) from the East Midlands of the United Kingdom were genotyped for seven polymorphisms. All cases were rheumatoid-factor positive. Significant genetic associations were observed with TNFR2 R-R (OR = 3.16, CI 1.20-9.26, P < 0.05), A2M 1-1 (OR = 2.09, CI 1.21-3.64, P < 0.05) and GST T(1)null (OR = 1.97, CI 1.07-3.68, P < 0.05) among Caucasian patients. In South Asians, VDR Bsm I B-B genotype (OR = 2.08, CI 1.23-3.52, P < 0.05), A2M 2-2 genotype (OR = 3.99, CI 1.19-17.18, P < 0.05), and GST T(1)null genotype (OR = 2.81, CI 1.40-5.77, P < 0.002) genotypes were associated with RA. In the majority of cases, recessive and multiplicative modes of inheritance explained the observed associations. This study demonstrates that ethnicity affects the genetic associations in RA.

The angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to rheumatoid arthritis, vitiligo and psoriasis: A meta-analysis

“…30 One eligible study contained data on two different RA groups, and these were treated independently. 21 Thus, a total of 15 separate comparisons met our inclusion criteria. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] These studies comprised five each on psoriasis, vitiligo and RA.…”

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22]30 One study was excluded because it contained duplicate data. 30 One eligible study contained data on two different RA groups, and these were treated independently.…”

“…However, published results on the genetic association for the ACE I/D polymorphism are controversial and inconclusive. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] This may be due to small sample sizes, low statistical power, and/or clinical heterogeneity. In order to overcome the limitations of individual studies, resolve inconsistencies and reduce the likelihood that random errors are responsible for false-positive or false-negative associations, we employed meta-analysis to further characterize the association.…”

A Possible Relationship Between Polymorphisms of Glutathione S-Transferase M1, P1 and T1 Genes and Rheumatoid Arthritis in Zahedan, Southeast Iran

“…[21] Furthermore, it has been demonstrated that in both Caucasian and South Asian populations, the GSTT1 null genotype, but not the GSTM1, is associated with RA. [1] Overall, although some small studies have examined the relationship between the polymorphisms of GSTs and the risk of RA, the association still remains unclear, and the debate continues. The reason for the controversial results of these studies could be associated with the differences in the populations studied and their exposures to agents related to RA development.…”

“…Both genetic and environmental factors have been shown to be relevant, contributory factors to the expression and complications of this disease. [1,2] The prevalence of RA is about 1% of the total population, and genetic factors have been estimated to account for 60% of the disease risk. [3] Glutathione S-transferase (GST) genes, known as a superfamily of phase II metabolic enzymes, catalyze the detoxification of xenobiotics via glutathione conjugation.…”