Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same diseaseReport as inadecuate




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Arthritis Research and Therapy

, 14:R239

First Online: 03 November 2012Received: 25 May 2012Revised: 23 September 2012Accepted: 30 October 2012

Abstract

IntroductionThe largest genetic risk to develop rheumatoid arthritis RA arises from a group of alleles of the HLA DRB1 locus -shared epitope-, SE. Over 30 non-HLA single nucleotide polymorphisms SNPs predisposing to disease have been identified in Caucasians, but they have never been investigated in West-Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans.

MethodsRA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria YRI, HapMap. A Caucasian aggregate genetic-risk score GRS was calculated as the sum of the weighted risk-allele counts.

ResultsAfter genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies MAF were tightly correlated between Cameroonian controls and YRI individuals correlation coefficient 93.8%, p = 1.7E-13, and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2-IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456. Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001.

ConclusionsThe MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West-Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds.

Abbreviationsanti-CCPanti-cyclic citrullinated peptide antibody

CEUUtah residents with ancestry from northern and western Europe

CIconfidence interval

GRSgenetic risk score

GWASgenome-wide association study

LDlinkage disequilibrium

LWKLuhya individuals in Webuye: Kenya

MAFminor allele frequency

ORodds ratio

RArheumatoid arthritis

SEshared epitope

SNPsingle-nucleotide polymorphism

UKRAGUnited Kingdom Rheumatoid Arthritis Genetics Consortium

YRIYoruba in Ibadan: Nigeria.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4082 contains supplementary material, which is available to authorized users.

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Author: Sebastien Viatte - Edward Flynn - Mark Lunt - Joanne Barnes - Madeleine Singwe-Ngandeu - Sylvette Bas - Anne Barton - Cem 

Source: https://link.springer.com/







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