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

Rector Arya, Agustin Escalante, Vidya S. Farook, Jose F. Restrepo, Daniel F. Battafarano, Marcio Almeida, Mark Z. Kos, Marcel J. Fourcaudot, Srinivas Mummidi, Satish Kumar, Joanne E. Curran, Christopher P. Jenkinson, John Blangero, Ravindranath Duggirala, Inmaculada del Rincon

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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.

LanguageEnglish (US)
Pages92-101
Number of pages10
JournalAtherosclerosis
Volume271
DOIs
StatePublished - Apr 1 2018

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Carotid Intima-Media Thickness
Genetic Association Studies
Rheumatoid Arthritis
Single Nucleotide Polymorphism
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 7
Genes
Atherosclerosis
Phenotype

Keywords

  • Carotid plaque
  • Genes
  • Genetic association
  • Single nucleotide polymorphisms
  • Subclinical atherosclerosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis. / Arya, Rector; Escalante, Agustin; Farook, Vidya S.; Restrepo, Jose F.; Battafarano, Daniel F.; Almeida, Marcio; Kos, Mark Z.; Fourcaudot, Marcel J.; Mummidi, Srinivas; Kumar, Satish; Curran, Joanne E.; Jenkinson, Christopher P.; Blangero, John; Duggirala, Ravindranath; del Rincon, Inmaculada.

In: Atherosclerosis, Vol. 271, 01.04.2018, p. 92-101.

Research output: Contribution to journalArticle

Arya, R, Escalante, A, Farook, VS, Restrepo, JF, Battafarano, DF, Almeida, M, Kos, MZ, Fourcaudot, MJ, Mummidi, S, Kumar, S, Curran, JE, Jenkinson, CP, 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, vol. 271, pp. 92-101. https://doi.org/10.1016/j.atherosclerosis.2017.11.024
Arya, Rector ; Escalante, Agustin ; Farook, Vidya S. ; Restrepo, Jose F. ; Battafarano, Daniel F. ; Almeida, Marcio ; Kos, Mark Z. ; Fourcaudot, Marcel J. ; Mummidi, Srinivas ; Kumar, Satish ; Curran, Joanne E. ; Jenkinson, Christopher P. ; Blangero, John ; Duggirala, Ravindranath ; del Rincon, Inmaculada. / A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis. In: Atherosclerosis. 2018 ; Vol. 271. pp. 92-101.
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T1 - A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis

AU - Arya, Rector

AU - Escalante, Agustin

AU - Farook, Vidya S.

AU - Restrepo, Jose F.

AU - Battafarano, Daniel F.

AU - Almeida, Marcio

AU - Kos, Mark Z.

AU - Fourcaudot, Marcel J.

AU - Mummidi, Srinivas

AU - Kumar, Satish

AU - Curran, Joanne E.

AU - Jenkinson, Christopher P.

AU - Blangero, John

AU - Duggirala, Ravindranath

AU - del Rincon, Inmaculada

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N2 - 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.

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KW - Carotid plaque

KW - Genes

KW - Genetic association

KW - Single nucleotide polymorphisms

KW - Subclinical atherosclerosis

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