Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis

Authors

Rector Arya, The University of Texas Rio Grande Valley
Inmaculada Del Rincon
Vidya S. Farook, The University of Texas Rio Grande Valley
Jose F. Restrepo
Marcio Almeida, The University of Texas Rio Grande Valley
Satish Kumar, The University of Texas Rio Grande Valley
Joanne E. Curran, The University of Texas Rio Grande Valley
Christopher Jenkinson, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
Ravi Duggirala, The University of Texas Rio Grande Valley
Agustin Escalante

Document Type

Article

Publication Date

10-26-2015

Abstract

Joint destruction in rheumatoid arthritis (RA) is heritable, but knowledge on specific genetic determinants of joint damage in RA is limited. We have used the Immunochip array to examine whether genetic variants influence variation in joint damage in a cohort of Mexican Americans (MA) and European Americans (EA) with RA. We studied 720 MA and 424 EA patients with RA. Joint damage was quantified using a radiograph of both hands and wrists, scored using Sharp's technique. We conducted association analyses with the transformed Sharp score and the Immunochip single nucleotide polymorphism (SNP) data using PLINK. In MAs, 15 SNPs from chromosomes 1, 5, 9, 17 and 22 associated with joint damage yielded strong p-values (p < 1 × 10−4). The strongest association with joint damage was observed with rs7216796, an intronic SNP located in the MAP3K14 gene, on chromosome 17 (β ± SE = −0.25 ± 0.05, p = 6.23 × 10−6). In EAs, 28 SNPs from chromosomes 1, 4, 6, 9, and 21 showed associations with joint damage (p-value < 1 × 10−4). The best association was observed on chromosome 9 with rs59902911 (β ± SE = 0.86 ± 0.17, p = 1.01 × 10−6), a synonymous SNP within the CARD9 gene. We also observed suggestive evidence for some loci influencing joint damage in MAs and EAs. We identified two novel independent loci (MAP3K14 and CARD9) strongly associated with joint damage in MAs and EAs and a few shared loci showing suggestive evidence for association.

Comments

© 2015 WILEY PERIODICALS, INC.

https://onlinelibrary.wiley.com/share/QPNYCTIP2N6BPEWVDDSE?target=10.1002/gepi.21938

Recommended Citation

Arya, R., del Rincon, I., Farook, V.S., Restrepo, J.F., Winnier, D.A., Fourcaudot, M.J., Battafarano, D.F., de Almeida, M., Kumar, S., Curran, J.E., Jenkinson, C.P., Blangero, J., Duggirala, R. and Escalante, A. (2015), Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis. Genet. Epidemiol., 39: 678-688. https://doi.org/10.1002/gepi.21938

Publication Title

Genetic Epidemiology

DOI

10.1002/gepi.21938

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics