TY - JOUR
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
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/4
Y1 - 2018/4
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.
AB - 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.
KW - Carotid plaque
KW - Genes
KW - Genetic association
KW - Single nucleotide polymorphisms
KW - Subclinical atherosclerosis
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U2 - 10.1016/j.atherosclerosis.2017.11.024
DO - 10.1016/j.atherosclerosis.2017.11.024
M3 - Article
C2 - 29482039
AN - SCOPUS:85042367944
SN - 0021-9150
VL - 271
SP - 92
EP - 101
JO - Atherosclerosis
JF - Atherosclerosis
ER -