A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis

Authors

Rector Arya, The University of Texas Rio Grande Valley
Agustin Escalante
Vidya S. Farook
Jose F. Restrepo
Daniel F. Battafarano
Marcio Almeida, The University of Texas Rio Grande Valley
Mark Kos, The University of Texas Rio Grande Valley
Marcel Fourcaudot
Srinivas Mummidi, 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
Inmaculada Del Rincon

Document Type

Article

Publication Date

4-2018

Abstract

Background and aims: Little is known about specific genetic determinants of carotid-intima-media thickness (CIMT) and carotid plaque in subjects with rheumatoid arthritis (RA). We have used the Metabochip array to fine map and replicate loci that influence variation in these phenotypes in Mexican Americans (MAs) and European Americans (EAs).

Methods: CIMT and plaque were measured using ultrasound from 700 MA and 415 EA patients with RA and we conducted association analyses with the Metabochip single nucleotide polymorphism (SNP) data using PLINK.

Results: In MAs, 12 SNPs from 11 chromosomes and 6 SNPs from 6 chromosomes showed suggestive associations (p < 1 × 10-4) with CIMT and plaque, respectively. The strongest association was observed between CIMT and rs17526722 (SLC17A2 gene) (β ± SE = -0.84 ± 0.18, p = 3.80 × 10-6). In EAs, 9 SNPs from 7 chromosomes and 7 SNPs from 7 chromosomes showed suggestive associations with CIMT and plaque, respectively. The top association for CIMT was observed with rs1867148 (PPCDC gene, β ± SE = -0.28 ± 0.06, p = 5.11 × 10-6). We also observed strong association between plaque and two novel loci: rs496916 from COL4A1 gene (OR = 0.51, p = 3.15 × 10-6) in MAs and rs515291 from SLCA13 gene (OR = 0.50, p = 3.09 × 10-5) in EAs.

Conclusions: We identified novel associations between CIMT and variants in SLC17A2 and PPCDC genes, and between plaque and variants from COL4A1 and SLCA13 that may pinpoint new candidate risk loci for subclinical atherosclerosis associated with RA.

Recommended Citation

Arya, R., Escalante, A., Farook, V. S., Restrepo, J. F., Battafarano, D. F., Almeida, M., Kos, M. Z., Fourcaudot, M. J., Mummidi, S., Kumar, S., Curran, J. E., Jenkinson, C. P., Blangero, J., Duggirala, R., & Del Rincon, I. (2018). A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis. Atherosclerosis, 271, 92–101. https://doi.org/10.1016/j.atherosclerosis.2017.11.024

Publication Title

Atherosclerosis

DOI

10.1016/j.atherosclerosis.2017.11.024

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics