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
RR
95% 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)
—
—
1.10
0.86 to 1.41
0.32
GG versus CC (as referent)
—
—
1.13
0.72 to 1.78
0.44
GC versus CC (as referent)
—
—
1.02
0.63 to 1.68
0.67
Genetic models
Dominant model (GG versus GC + CC as referent)
—
—
1.12
0.88 to 1.41
0.25
Recessive model (GG + GC versus CC as referent)
—
—
1.10
0.70 to 1.72
0.50
Alleles 2n = 110
2n = 96
2n = 14
G allele, (%)
74 (89.2)
9 (10.8)
1.09
0.90 to 1.33
0.20
C allele, (%)
22 (81.5)
5 (18.5)
Referent
—
Follow-up at 6 months
MTX nonresponse
MTX response
RR
95% 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)
—
—
0.99
0.80 to 1.23
0.67
GG versus CC (as referent)
—
—
1.09
0.68 to 1.73
0.52
GC versus CC (as referent)
—
—
1.10
0.68 to 1.76
0.55
Genetic models
Dominant model (GG versus GC + CC as referent)
—
—
1.01
0.82 to 1.25
0.58
Recessive model (GG + GC versus CC as referent)
—
—
1.10
0.70 to 1.72
0.50
Alleles, 2n = 110
2n = 96
2n = 14
G allele, (%)
73 (88.0)
10 (12.0)
1.03
0.86 to 1.23
0.35
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).