Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis.
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.
South Texas Diabetes and Obesity Institute and Regional Academic Health Center, the University of Texas Health Science Center, Edinburg, Texas, United States of America.
Rector
R
Arya
Division of Rheumatology and Clinical Immunology, Department of Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
Inmaculada
I
Del Rincon
South Texas Diabetes and Obesity Institute and Regional Academic Health Center, the University of Texas Health Science Center, Edinburg, Texas, United States of America.
Vidya S
VS
Farook
Division of Rheumatology and Clinical Immunology, Department of Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
Jose F
JF
Restrepo
Research and Information Management, University Health System, San Antonio, Texas, United States of America.
Diedre A
DA
Winnier
Division of Diabetes, Department of Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
Marcel J
MJ
Fourcaudot
Brook Army Medical Center, Fort Sam Houston, Texas, United States of America.
Daniel F
DF
Battafarano
South Texas Diabetes and Obesity Institute and UT Brownsville, Brownsville, Texas, United States of America.
Marcio
M
de Almeida
South Texas Diabetes and Obesity Institute and Regional Academic Health Center, the University of Texas Health Science Center, Edinburg, Texas, United States of America.
Satish
S
Kumar
South Texas Diabetes and Obesity Institute and UT Brownsville, Brownsville, Texas, United States of America.
Joanne E
JE
Curran
South Texas Diabetes and Obesity Institute and Regional Academic Health Center, the University of Texas Health Science Center, Edinburg, Texas, United States of America.
Christopher P
CP
Jenkinson
South Texas Diabetes and Obesity Institute and UT Brownsville, Brownsville, Texas, United States of America.
John
J
Blangero
South Texas Diabetes and Obesity Institute and Regional Academic Health Center, the University of Texas Health Science Center, Edinburg, Texas, United States of America.
Ravindranath
R
Duggirala
Division of Rheumatology and Clinical Immunology, Department of Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
Agustin
A
Escalante
D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007596:Joints / Q000473:pathology*; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics; D000097782:NF-kappaB-Inducing Kinase
D053468:CARD Signaling Adaptor Proteins; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C505855:CARD9 protein, human
European Americans; Mexican Americans; genetic association; joint damage; rheumatoid arthritis susceptibility loci