Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

MMEL1 and CDK6 Are Associated with ACPA Positive and RF Positive Rheumatoid Arthritis.

Maehlen1,  Marthe Thoresen, Kvien3,  Tore K., Uhlig2,  Till, Lie4,  Benedicte A.

Dept. of Rheumatology, Diakonhjemmet Hospital, 2. Institute of Immunology, Oslo University Hospital, Oslo, Oslo, Norway
Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
Diakonhjemmet Hospital, Oslo, Norway
Institute of Immunology, Oslo University Hospital, Oslo, Norway


Genes play an important role in the aetiology of rheumatoid arthritis (RA), and recent genome wide association studies have reported several new SNPs to be associated with RA. Some of these have been replicated. However, further studies are needed to establish whether these are true risk loci.


Investigate whether 11 candidate SNPs (in KIF5A, REL, CCL21, PRKCQ, STAT4, CTLA4, MMEL1, CDK6, TRAF1, OLIG3-TNFAIP3 (2 SNPs)) are associated with RA and autoantibody production in the Norwegian population.


DNA from 950 Norwegian RA patients and 1130 Norwegian controls were genotyped with TaqMan assays (Applied Biosystems). All 11 SNPs had >98% genotyping success rate and all genotypes were in Hardy-Weinberg equilibrium. c2 tests were used to test for associations. For the SNPs that were not associated with RA, we calculated the power in our dataset to detect an association using Power and Sample Size program, version PS 3.0.14. These calculations were based on odds ratios and minor allele frequencies published in a recent meta-analysis (Stahl, E.A. et al Nat. Genet, 2010).


The major allele of MMEL1 and minor allele of CDK6 were both significantly associated with RA (table). The associations were restricted to ACPA positive and RF positive RA. The minor allele of STAT 4 was significantly associated with ACPA positive RA only. None of these 3 SNPs were associated with ACPA negative or RF negative RA. The remaining eight SNPs showed no significant association with RA in our Norwegian cohort.

GenePatientsMinor alleleMAF caseMAF controlAllele testOR 95% CIP-value
MMEL1ALLC0.2980.334T/C1.18 (1.03–1.35)0.01
MMEL1ACPA +C0.2760.334T/C1.30 (1.11–1.53)0.001
MMEL1RF +C0.2510.334T/C1.45 (1.26–1.78)>0.001
CDK6ALLG0.2620.227G/C1.20 (1.04–1.39)0.01
CDK6ACPA +G0.2740.227G/C1.28 (1.09–1.52)0.003
CDK6RF+G0.2780.227G/C1.31 (1.10–1.56)0.003
STAT4ALLT0.2390.223T/G1.10 (0.95–1.27)0.22
STAT4ACPA+T0.2530.223T/G1.18 (1.0–1.40)0.05


We replicated the proposed associations between MMEL1 and CDK6 with RA. In addition we demonstrated that CDK6 and MMEL1 are associated to both ACPA positive and RF positive RA. Further we confirmed that STAT4 is associated with ACPA positive RA. We found no association with eight SNPs, however due to moderate to low risk in other populations, we may have had insufficient power to detect an association.

To cite this abstract, please use the following information:
Maehlen, Marthe Thoresen, Kvien, Tore K., Uhlig, Till, Lie, Benedicte A.; MMEL1 and CDK6 Are Associated with ACPA Positive and RF Positive Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1603
DOI: 10.1002/art.29369

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