Table 1 shows the sociodemographic and clinical data of the patients with PsO and controls. The patients were older (p < 0.001) and had higher BMI (p < 0.001) than controls. As expected, there were no significant differences in sex (p = 0.013) and ethnicity (p < 0.781) between both study groups; 95.8% of the patients had plaque PsO and 16.1% had PsA; 43 patients (27.9%) had PASI > 10 with median of 5.1 (11.1–29.3). In relation to treatment, 55.8% were under systemic treatment while 40.3% were using topical therapy.
Table 1
Sociodemographic and clinical data of patients with psoriasis and controls
|
Controls
(n = 154)
|
Psoriasis
(n = 154)
|
p-value*
|
Age (Years)
|
36 (29–44)
|
54 (44–63)
|
< 0.001
|
Sex (Female/Male)
|
87 (56.5)/ 67 (43.5)
|
74 (48.1)/ 80 (51.9)
|
0.138
|
Ethnicity (Caucasian/Non-Caucasian)
|
120 (77.9)/ 34 (22.1)
|
122 (79.2)/ 32 (20.8)
|
0.781
|
Body mass index (kg/cm2)
|
25.17 (22.27–28.58)
|
29.88 (26.22–33.02)
|
< 0.001
|
Plaque psoriasis
|
-
|
137 (95.8)
|
-
|
Psoriatic arthritis
|
-
|
23 (16.1)
|
-
|
PASI Score
|
-
|
5.1 (11.1–29.3)
|
-
|
PASI ≥ 10
|
-
|
43 (27.9)
|
-
|
Systemic treatment
|
-
|
86 (55.8)
|
-
|
Topic treatment
|
-
|
62 (40.3)
|
-
|
Bold values represent statistically significant values; χ2 test. Data were expressed by absolute number (%). Mann-Whitney test. Data were expressed as median and percentile (25–75%). PASI: Psoriasis Area and Severity Index |
Table 2 shows the two SNV of IL36G (rs13392494 and rs7584409) divided into four genetic models (dominant, codominant, overdominant, and recessive) to assess their association with PsO susceptibility. The HWE of rs13392494 and rs7584409 were observed among the PsO patients and controls and were consistent with the expected (p > 0.05). Regarding the IL36G rs1339294 variant, no significant association was found between the allele frequencies (OR 0.938, 95% CI 0.625–1.404, p = 0.758) and the PsO. In addition, the frequency of the CC, CT, and TT genotypes (codominant, dominant, recessive, and overdominant genetic models) also did not differ between PsO patients and controls (p > 0.05). Regarding the IL36G rs7584409 variant, no significant association was found between the allele frequencies (OR 0.887, 95% CI 0.617–1.271, p = 0.517) and the PsO. However, the frequency of AA, AG, and GG genotypes differed between PsO patients and controls in the dominant genetic model. The AG + GG genotypes were associated with lower odds for PsO diagnosis than the AA genotype (OR 0.525, 95% CI 0.283–0.975, p = 0.041). When the overdominant and recessive genetics models were evaluated, no significant association were observed (p > 0.05). All data showed in the Table 2 were adjusted by age, sex, ethnicity, and BMI.
Table 2
Distribution of genotypes and allele frequencies of IL36G single nucleotide variants in Brazilian patients with psoriasis and healthy controls
Model
|
|
Controls
(n = 154)
|
Psoriasis
(n = 154)
|
OR (95% CI)
|
p-value
|
IL36G rs13392494 (C > T)
|
|
|
|
|
Allelic
|
C
|
248 (80.52)
|
251 (81.49)
|
Reference
|
-
|
|
T
|
60 (19.48)
|
57 (18.51)
|
0.938 (0.625–1.404)
|
0.758
|
Codominant
|
CC
|
98 (63.6)
|
103 (66.9)
|
Reference
|
-
|
|
CT
|
52 (33.8)
|
45 (29.2)
|
0.938 (0.501–1.755)
|
0.841
|
|
TT
|
4 (2.6)
|
6 (3.9)
|
1.413 (0.273–7.315)
|
0.680
|
Dominant
|
CC
|
98 (63.6)
|
103 (66.9)
|
Reference
|
-
|
|
CT + TT
|
56 (36.4)
|
51 (33.1)
|
0.973 (0.529–1.788)
|
0.929
|
Recessive
|
CC + CT
|
150 (97.4)
|
148 (96.1)
|
Reference
|
-
|
|
TT
|
4 (2.6)
|
6 (3.9)
|
1.447 (0.284–7.369)
|
0.657
|
Overdominant
|
CC + TT
|
102 (66.2)
|
109 (70.8)
|
Reference
|
-
|
|
CT
|
52 (33.8)
|
45 (29.2)
|
0.921 (0.495–1.712)
|
0.794
|
IL36G rs7584409 (A > G)
|
Allelic
|
A
|
226 (73.38)
|
233 (75.65)
|
Reference
|
-
|
|
G
|
82 (26.62)
|
75 (24.35)
|
0.887 (0.617–1.271)
|
0.517
|
Codominant
|
AA
|
86 (55.8)
|
91 (59.1)
|
Reference
|
-
|
|
AG
|
54 (35.1)
|
51 (33.1)
|
0.575 (0.296–1.116)
|
0.102
|
|
GG
|
14 (9.1)
|
12 (7.8)
|
0.375 (0.123–1.140)
|
0.084
|
Dominant
|
AA
|
86 (55.8)
|
91 (59.1)
|
Reference
|
-
|
|
AG + GG
|
68 (44.2)
|
63 (40.9)
|
0.525 (0.283–0.975)
|
0.041
|
Recessive
|
AA + AG
|
140 (90.9)
|
142 (92.2)
|
Reference
|
-
|
|
GG
|
14 (9.1)
|
12 (7.8)
|
0.458 (0.157–1.342)
|
0.155
|
Overdominant
|
AA + GG
|
100 (64.9)
|
103 (66.9)
|
Reference
|
-
|
|
AG
|
54 (35.1)
|
51 (33.1)
|
0.654 (0.344–1.244)
|
0.195
|
Bold values represent statistically significant values; χ2: results of analyses of contingency tables. Data were expressed as absolute number (n) and percentage (%). OR: odds ratio; CI: confidence interval. Results of logistic regression analysis adjusted by age, sex, ethnicity, and body mass index. |
Four possible haplotype combinations with IL36G rs1339294 (C > T) and IL36G rs7584409 (A > G) variants were investigated in our study: C/A, C/G, T/A, and T/G. The predominant haplotype was C/A (79.2%, dominant model) while no individual with T/G haplotype was found. In the association study of the IL36G haplotypes, the following genetic models were analyzed: C/A dominant (C/A carriers versus C/G and T/A carriers), C/A recessive (CACA versus C/G and T/A carriers), C/G dominant (C/G carriers versus C/A and T/A carriers), C/G recessive (CGCG carriers versus C/A and T/A carriers), T/A dominant (T/A carriers versus C/A and C/G carriers), and T/A recessive (TATA carriers versus C/A and C/G carriers). Table 3 shows the distribution of IL36G rs13392494 and IL36G rs7584409 haplotypes among PsO patients and controls. We found an association between the CACA haplotype (recessive model) with PsO (OR 1.995, 95% CI 1.050–3.788, p = 0.035) adjusted by age, sex, ethnicity, and BMI. On the other hand, we found a protective effect of the C/G haplotype (dominant genetic model) with PsO (OR 0.525, 95% CI 0.283–0.975, p = 0.041) adjusted by age, sex, ethnicity, and BMI.
Table 3
Distribution of the IL36G rs13392494 (C > T) and IL36G rs7584409 (A > G) haplotypes among Brazilian patients with psoriasis and healthy controls
Haplotypes*
|
Controls
n (%)
|
Psoriasis
n (%)
|
OR (95% CI)
|
p-value
|
C/A dominant
|
122 (79.2)
|
122 (79.2)
|
1.417 (0.683–2.942)
|
0.349
|
C/A recessive
|
44 (28.6)
|
54 (35.1)
|
1.995 (1.050–3.788)
|
0.035
|
C/G dominant
|
68 (44.2)
|
63 (40.9)
|
0.525 (0.283–0.975)
|
0.041
|
C/G recessive
|
14 (9.1)
|
12 (7.8)
|
0.458 (0.157–1.342)
|
0.155
|
T/A dominant
|
56 (36.4)
|
51 (33.1)
|
0.973 (0.529–1.788)
|
0.929
|
T/A recessive
|
4 (2.6)
|
6 (3.9)
|
1.447 (0.284–7.369)
|
0.657
|
Bold values represent statistically significant values; OR (odds ratio) and CI (confidence interval) 95% estimated by binary logistic regression controlling by age, sex, ethnicity, and body mass index. |
* C/A dominant: C/A carriers versus C/G and T/A carriers; C/A recessive: CACA versus C/G and T/A carriers; C/G dominant: C/G carriers versus C/A and T/A carriers; C/G recessive: CGCG carriers versus C/A and T/A carriers; T/A dominant: T/A carriers versus C/A and C/G carriers; T/A recessive: TATA carriers versus C/A and C/G carriers; the T/G haplotype was not found in the cohort of the study. |
We used different regression analyses models to delineate whether these IL36G variants were independently associated with PASI score and the presence of PsA. Table 4 shows the results of binary logistic regression analysis with moderate to severe disease (PASI > 10) as dependent variable and those in remission or mild severity (PASI ≤ 10) as reference group. The presence of G allele of IL36G rs7584409, in heterozygosis and homozygosis (AG + GG group), was positively associated with PASI > 10 (OR 2.311, 95% CI 1.079–4.951, p = 0.031), independently of sex, ethnicity, and age (regression #1). On the other hand, CACA haplotype was negatively associated with PASI score (OR 0.418, 95% CI 0.182–0.962, p = 0.040), independently of sex, ethnicity, and age (regression #2).
Table 4
Result of binary logistic regression analysis with an increased PASI score (> 10) as dependent variable and those with lower PASI score (≤ 10) as reference group
Regression
|
Explanatory Variables
|
Wald
|
df
|
p value
|
OR
|
95% CI
|
#1
|
Age
|
3.292
|
1
|
0.070
|
0.975
|
0.948–1.002
|
|
Sex
|
0.044
|
1
|
0.833
|
1.083
|
0.515–2.280
|
|
Ethnicity
|
0.002
|
1
|
0.963
|
1.022
|
0.402–2.599
|
|
IL36G rs7584409 A > G
|
4.646
|
1
|
0.031
|
2.311
|
1.079–4.951
|
#2
|
Age
|
2.888
|
1
|
0.089
|
0.977
|
0.951–1.004
|
|
Sex
|
0.140
|
1
|
0.709
|
1.152
|
0.549–2.418
|
|
Ethnicity
|
0.164
|
1
|
0.685
|
0.825
|
0.326–2.087
|
|
CACA haplotype
|
4.208
|
1
|
0.040
|
0.418
|
0.182–0.962
|
PASI: Psoriasis Area and Severity Index; df: degree of freedom; OR: odds ratio; CI: confidence interval |
IL36G rs7584409 A > G: AA vs AG + GG (dominant model). |
CACA haplotype: CACA versus C/G and T/A carriers |
Table 5 shows the results of binary logistic regression analysis with PsA as dependent variable and genotypes, haplotypes, sex, ethnicity and age as covariates. Regression #1 shows that IL36G rs7584409 GG genotype was independently associated with the presence of PsA (OR 5.187, 95% CI 1.403–19.182, p = 0.014), while C/A dominant haplotype has a protective effect on PsA diagnosis (OR 0.324, 95% CI 0.123–0.857, p = 0.023).
Table 5
Result of binary logistic regression analysis and psoriatic arthritis as dependent variable
Regression
|
Explanatory Variables
|
Wald
|
df
|
p value
|
OR
|
95% CI
|
#1
|
Age
|
0.132
|
1
|
0.716
|
1.006
|
0.972–1.042
|
|
Sex
|
0085
|
1
|
0.770
|
0.870
|
0.341–2.217
|
|
Ethnicity
|
0.030
|
1
|
0.863
|
0.899
|
0.267–3.028
|
|
IL36G rs7584409 A > G
|
6.086
|
1
|
0.014
|
5.187
|
1.403–19.182
|
#2
|
Age
|
0.279
|
1
|
0.597
|
1.009
|
0.975–1.045
|
|
Sex
|
0.133
|
1
|
0.715
|
0.841
|
0.332–2.132
|
|
Ethnicity
|
0.151
|
1
|
0.697
|
0.788
|
0.237–2.619
|
|
C/A dominant haplotype
|
5.158
|
1
|
0.023
|
0.324
|
0.123–0.857
|
Df: degree of freedom; OR: odds ratio; CI: confidence interval; |
IL36G rs7584409 A > G: AA + AG vs GG (recessive model). |
C/A dominant haplotype: C/A carriers versus C/G and T/A carriers |