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 5
Evaluation of -174G/C IL-6 as predictor of therapeutic response to leflunomide (LEF) defining nonresponse, as DAS-28 > 3.2 at 3 or 6 months in rheumatoid arthritis (RA).
Treatment with leflunomide (LEF)
Follow-up at 3 months
LEF nonresponse
LEF response
RR
95% CI
Genotype
GG (%)
17 (81)
4 (19)
—
—
0.64
GC (%)
11 (78.6)
3 (21.4)
—
—
CC (%)
6 (17.6)
0 (0)
—
—
GG versus GC (as referent)
—
—
1.03
0.73 to 1.45
0.43
GG versus CC (as referent)
—
—
0.81
0.66 to 0.99
0.17
GC versus CC (as referent)
—
—
0.78
0.60 to 1.03
0.16
Genetic models
Dominant model (GG versus GC + CC as referent)
—
—
0.95
0.72 to 1.26
0.37
Recessive model (GG + GC versus CC as referent)
—
—
0.80
0.68 to 0.94
0.15
Alleles, 2n = 82
2n = 68
2n = 14
G allele, (%)
45 (80.4)
11 (19.6)
0.91
0.75 to 1.10
0.19
C allele, (%)
23 (88.5)
3 (11.5)
Referent
—
Follow-up at 6 months
LEF nonresponse
LEF response
RR
95% CI
Genotype
GG (%)
21 (100)
0 (0)
—
—
0.006
GC (%)
9 (25)
5 (100)
—
—
CC (%)
6 (16.7)
0 (0)
—
—
GG versus GC (as referent)
—
—
1.56
1.05 to 2.30
0.003
GG versus CC (as referent)
—
—
1.83
1.07 to 3.14
0.001
GC versus CC (as referent)
—
—
0.64
0.43 to 0.95
0.06
Genetic models
Dominant model (GG versus GC + CC as referent)
—
—
1.33
1.03 to 1.72
0.02
Recessive model (GG + GC versus CC as referent)
—
—
0.86
0.75 to 0.98
0.43
Alleles, 2n = 82
2n = 72
2n = 10
G allele, (%)
51 (91.1)
5 (8.9)
1.13
0.92 to 1.38
0.11
C allele, (%)
21 (81.0)
5 (19.0)
Referent
—
LEF: leflunomide; GG: excisable homozygote genotype (); GC: heterozygote genotype (); CC: homozygote genotype (). Qualitative variables were expressed in frequencies (%); quantitative variables were expressed as means ± standard deviations (SD). RR: Relative Risk; 95% CI: 95% Confidence Intervals. Therapeutic failure (nonresponse) was defined if patients did not achieve remission or low disease activity (DAS-28 < 3.2).
