Clinical Study

The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis

Table 4

Evaluation of -174G/C IL-6 as predictor of therapeutic response to methotrexate (MTX) defining nonresponse, as DAS-28 > 3.2 at 3 or 6 months in rheumatoid arthritis (RA).

Treatment with methotrexate (MTX), ⁢⁢⁢Follow-up at 3 months
MTX
nonresponse
MTX
response
RR95% CI

Genotype
GG (%)30 (90.9)3 (9.1)0.60
GC (%)14 (82.4)3 (17.6)
CC (%)4 (80)1 (20)
GG versus GC (as referent)1.100.86 to 1.410.32
GG versus CC (as referent)1.130.72 to 1.780.44
GC versus CC (as referent)1.020.63 to 1.680.67
Genetic models
Dominant model (GG versus GC + CC as referent)1.120.88 to 1.410.25
Recessive model (GG + GC versus CC as referent)1.100.70 to 1.720.50
Alleles 2n = 1102n = 962n = 14
G allele, (%)74 (89.2)9 (10.8)1.090.90 to 1.330.20
C allele, (%)22 (81.5)5 (18.5)Referent

⁢Follow-up at 6 months
MTX
nonresponse
MTX
response
RR95% CI

Genotype
GG (%)29 (87.9)4 (12.1)0.87
GC (%)15 (88.2)2 (11.8)
CC (%)4 (80)1 (20)
GG versus GC (as referent)0.990.80 to 1.230.67
GG versus CC (as referent)1.090.68 to 1.730.52
GC versus CC (as referent)1.100.68 to 1.760.55
Genetic models
Dominant model (GG versus GC + CC as referent)1.010.82 to 1.250.58
Recessive model (GG + GC versus CC as referent)1.100.70 to 1.720.50
Alleles, 2n = 1102n = 962n = 14
G allele, (%)73 (88.0)10 (12.0)1.030.86 to 1.230.35
C allele, (%)23 (85.2)4 (14.8)Referent

MTX: methotrexate; GG: excisable homozygote genotype; GC: heterozygote genotype; CC: homozygote genotype. Qualitative variables were expressed in frequencies (%); RR: Relative Risk; 95% CI: 95% Confidence Interval. Therapeutic failure (nonresponse) was defined if patients did not achieve remission or low disease activity (DAS-28 < 3.2).