Association of IL-17 and IL-23 Gene Variants with Plasma Levels and Risk of Vulvovaginal Candidiasis in a Chinese Han Population

Figures & data

Table 1 Patient Demographics and Risk Factors in Vulvovaginal Candidiasis

Characteristics	Case (N=217)	Control (N=326)	P
Age	33.03±7.82	32.08±8.16	0.180
Smoking			0.558
Yes	75 (34.6%)	105 (32.2%)
No	142 (65.4%)	221 (67.8%)
Drinking			0.811
Yes	68 (31.3%)	99 (30.4%)
No	149 (68.7%)	227 (69.6%)
BMI	23.61±2.71	23.51±3.05	0.704
Number of children	1.47±1.13	1.00±0.85	0.000
Number of miscarriages	1.05±0.80	0.16±0.37	0.000
Family history of VVC	28 (12.9%)	13 (4.0%)	0.000
Disease types
RVVC	46 (21.2%)
VVC	171 (78.8%)

Note: Bold values are statistically significant (P <0.05).

Abbreviations: RVVC, recurrent vulvovaginal candidiasis; VVC, vulvovaginal candidiasis.

Table 2 Genotype Frequencies of IL-23R and IL-17 Gene Polymorphisms in Cases and Controls

Models	Genotype	Case (n, %)^a	Control (n, %)^a	OR (95% CI)	P-value	*OR (95% CI)	*P-value
rs11209026
Co-dominant	GG	163 (75.1%)	269 (82.5%)	1.00 (reference)
Heterozygote	GA	50 (23.0%)	53 (16.3%)	1.56 (1.01–2.40)	0.044	1.58 (1.02–2.43)	0.043
Homozygote	AA	4 (1.8%)	4 (1.2%)	1.65 (0.41–6.69)	0.733	1.63 (0.40–6.65)	0.721
Dominant	GG	163 (75.1%)	269 (82.5%)	1.00 (reference)
	AA+GA	54 (24.9%)	57 (17.5%)	1.56 (1.03–2.38)	0.036	1.53 (1.02–2.35)	0.032
Recessive	GA+GG	213 (98.1%)	322 (98.8%)	1.00 (reference)
	AA	4 (1.8%)	4 (1.2%)	1.51 (0.37–6.11)	0.826	1.54 (0.33–6.13)	0.831
Allele	G	376 (86.6%)	591 (90.6%)	1.00 (reference)
	A	58 (13.3%)	61 (9.3%)	1.50 (1.02–2.19)	0.038
rs2275913
Co-dominant	GG	85 (36.9%)	161 (49.4%)	1.00 (reference)
Heterozygote	GA	102 (47.0%)	136 (41.7%)	1.42 (0.98–2.05)	0.061	1.41 (0.97–2.02)	0.059
Homozygote	AA	30 (13.8%)	29 (8.9%)	1.96 (1.10–3.48)	0.020	1.94 (1.12–3.46)	0.017
Dominant	GG	85 (39.1%)	161 (49.4%)	1.00 (reference)
	AA+GA	132 (60.8%)	165 (50.6%)	1.52 (1.07–2.15)	0.019	1.51 (1.05–2.14)	0.018
Recessive	GA+GG	187 (86.2%)	297 (91.1%)	1.00 (reference)
	AA	30 (13.8%)	29 (8.9%)	1.64 (0.96–2.83)	0.071	1.63 (0.94–2.81)	0.067
Allele	G	272 (62.7%)	458 (70.2%)	1.00 (reference)
	A	162 (37.3%)	194 (29.7%)	1.41 (1.09–1.82)	0.009
rs763780
Co-dominant	TT	120 (55.3%)	213 (65.3%)	1.00 (reference)	–
Heterozygote	TC	83 (38.2%)	101 (31.0%)	1.46 (1.01–2.10)	0.043	1.44 (1.02–2.08)	0.041
Homozygote	CC	14 (6.4%)	12 (3.7%)	2.07 (0.93–4.62)	0.071	2.05 (0.92–4.60)	0.069
Dominant	TT	120 (55.3%)	213 (65.3%)	1.00 (reference)	–
	CC+TC	97 (44.7%)	113 (34.7%)	1.52 (1.07–2.17)	0.019	1.51 (1.05–2.15)	0.017
Recessive	TT+TC	203 (93.5%)	314 (96.3%)	1.00 (reference)	–
	CC	14 (6.5%)	12 (3.7%)	1.81 (0.82–3.98)	0.139	1.80 (0.81–3.95)	0.136
Allele	T	323 (74.4%)	527 (80.8%)	1.00 (reference)	–
	C	111 (25.6%)	125 (19.2%)	1.45 (1.08–1.94)	0.012

Notes: ^aRs11209026, rs2275913 and rs763780 polymorphisms were successfully genotyped for all individuals; Bold values are statistically significant (P < 0.05); *Adjust for age, smoking and drinking.

Table 3 Stratified Analyses Between IL-23R and IL-17 Gene Polymorphisms and the Risk of Vulvovaginal Candidiasis

Variables	Genotypes (Case/Control)			Heterozygous Model	Homozygous Model	Recessive Model	Dominant Model
	Wild	Heterozygote	Homozygous
rs11209026	GG	GA	AA	GA vs GG	AA vs GG	AA vs GG+GA	AA+GA vs GG
BMI (kg/m^2)
<25	115/187	35/43	3/2	1.32 (0.80–2.19); 0.274	2.44 (0.40–14.82); 0.592	2.30 (0.38–13.93); 0.637	1.37 (0.84–2.42); 0.204
≥25	48/82	15/10	1/2	2.56 (1.07–6.15); 0.031	0.85 (0.08–9.67); 1.000	0.73 (0.07–8.23); 1.000	1.95 (0.86–4.40); 0.105
Smoking
Yes	50/87	23/16	2/2	2.50 (1.21–5.17); 0.012	1.74 (0.24–12.74); 0.979	1.41 (0.19–10.25); 1.000	2.42 (1.20–4.86); 0.012
No	113/182	27/37	2/2	1.18 (0.68–2.04); 0.564	1.61 (0.22–11.60); 1.000	1.56 (0.22–11.23); 1.000	1.44 (0.85–2.45); 0.176
Drinking
Yes	46/77	21/20	1/2	1.76 (0.86–3.59); 0.119	0.84 (0.07–9.49); 1.000	0.73 (0.06–8.15); 1.000	1.67 (0.84–3.35); 0.144
No	117/192	29/33	3/2	1.44 (0.83–2.50); 0.190	2.46 (0.41–14.95); 0.585	2.31 (0.38–14.00); 0.633	1.50 (0.88–2.55); 0.133
Age (years)
<30	60/116	18/23	3/2	1.51 (0.76–3.02); 0.238	2.90 (0.47–17.83); 0.470	2.67 (0.44–16.34); 0.269	1.62 (0.84–3.14); 0.147
≥30	103/153	32/30	1/2	1.58 (0.91–2.77); 0.104	0.74 (0.07–8.30); 1.000	0.68 (0.06–7.55); 1.000	1.53 (0.89–2.65); 0.125
rs2275913	GG	GA	AA	GA vs GG	AA vs GG	AA vs GG+GA	AA+GA vs GG
BMI (kg/m^2)
<25	57/101	75/110	21/21	1.21 (0.78–1.87); 0.397	1.77 (0.89–3.52); 0.100	1.60 (0.84–3.04); 0.150	1.30 (0.86–1.97); 0.220
≥25	28/60	27/26	9/8	2.23 (1.10–4.49); 0.024	2.41 (0.84–6.91); 0.095	1.76 (0.64–4.83); 0.269	2.27 (1.19–4.34); 0.013
Smoking
Yes	28/54	35/43	12/8	1.57 (0.83–2.97); 0.165	2.89 (1.06–7.90); 0.034	2.31 (0.89–5.97); 0.078	1.78 (0.97–3.25); 0.061
No	57/107	67/93	18/21	1.35 (0.86–2.12); 0.187	1.61 (0.79–3.26); 0.185	1.38 (0.71–2.70); 0.341	1.40 (0.91–2.15); 0.122
Drinking
Yes	24/47	36/45	8/7	1.57 (0.81–3.03); 0.181	2.24 (0.73–6.91); 0.155	1.75 (0.60–5.09); 0.297	1.66 (0.88–3.13); 0.118
No	61/114	66/91	22/22	1.36 (0.87–2.11); 0.179	1.87 (0.96–3.64); 0.064	1.61 (0.86–3.03); 0.134	1.46 (0.96–2.21); 0.078
Age (years)
<30	31/69	35/56	15/16	1.39 (0.77–2.53); 0.279	2.09 (0.92–4.75); 0.076	1.78 (0.83–3.82); 0.138	1.55 (0.89–2.70); 0.124
≥30	54/92	67/80	15/13	1.43 (0.89–2.28); 0.135	1.97 (0.87–4.44); 0.100	1.64 (0.75–3.57); 0.209	1.50 (0.96–2.35); 0.075
rs763780	TT	TC	CC	TC vs TT	CC vs.TT	CC vs TT+TC	CC+TC vs TT
BMI (kg/m^2)
<25	89/147	53/76	11/9	1.15 (0.74–1.79); 0.527	2.02 (0.81–5.06); 0.128	1.92 (0.78–4.75); 0.152	1.24 (0.82–1.89); 0.306
≥25	31/66	30/25	3/3	2.56 (1.29–5.05); 0.006	2.13 (0.41–11.16); 0.642	1.49 (0.29–7.64); 0.953	2.51 (1.30–4.86); 0.006
Smoking
Yes	37/71	28/28	10/6	1.92 (0.99–3.70); 0.051	3.20 (1.08–9.49); 0.030	2.54 (0.88–7.32); 0.077	2.15 (1.17–3.95); 0.014
No	83/142	55/73	4/6	1.29 (0.83–2.01); 0.260	1.14 (0.31–4.16);1.000	1.04 (0.29–3.75); 1.000	1.28 (0.83–1.97); 0.266
Drinking
Yes	39/67	23/27	6/5	1.46 (0.74–2.89); 0.273	2.06 (0.59–7.20); 0.249	1.82 (0.53–6.22); 0.334	1.56 (0.82–2.95); 0.173
No	81/146	60/74	8/7	1.46 (0.95–2.26); 0.087	2.06 (0.72–5.89); 0.170	1.78 (0.63–5.03); 0.268	1.51 (0.99–2.31); 0.054
Age (years)
<30	51/94	24/43	6/4	1.03 (0.56–1.88); 0.927	2.77 (0.75–10.25); 0.217	2.74 (0.75–10.02); 0.213	1.18 (0.67–2.09); 0.577
≥30	69/119	59/58	8/8	2.03 (1.86–4.62); 0.000	2.88 (1.04–7.98); 0.067	1.38 (0.51–3.78); 0.526	1.75 (1.12–2.75); 0.015

Note: Bold values are statistically significant (P < 0.05).

Table 4 Genetic (G) and Environmental (E) Factors 2 × 4 Fork Analysis

G^a	E^b	Case	Control	OR (95% CI); P value	Reflecting Information
rs11209026
AA vs GG	Smoking
+	+	2	2	1.61 (0.22,11.60); 1.000	G, E combined effect
+	–	2	2	1.61 (0.22,11.60); 1.000	G alone effect
–	+	50	87	0.93 (0.61,1.41); 0.718	E alone effect
–	–	113	182	1.00 (reference)	Common control
GA vs GG	Smoking
+	+	23	16	2.32 (1.17,4.57); 0.014	G, E combined effect
+	–	27	37	1.18 (0.68,2.04); 0.564	G alone effect
–	+	50	87	0.93 (0.61,1.41); 0.718	E alone effect
–	–	113	182	1.00 (reference)	Common control
AA vs GG	Drinking
+	+	1	2	0.82 (0.07,9.15); 1.000	G, E combined effect
+	–	3	2	2.46 (0.41,14.95); 0.585	G alone effect
–	+	46	77	0.98 (0.64,1.51); 1.000	E alone effect
–	–	117	192	1.00 (reference)	Common control
GA vs GG	Drinking
+	+	21	20	1.72 (0.90,3.31); 0.100	G, E combined effect
+	–	29	33	1.44 (0.83,2.50); 0.190	G alone effect
–	+	46	77	0.98 (0.64,1.51); 1.000	E alone effect
–	–	117	192	1.00 (reference)	Common control
rs2275913
AA vs GG	Smoking
+	+	12	8	2.82 (1.09,7.29); 0.028	G, E combined effect
+	–	18	21	1.61 (0.79,3.26); 0.185	G alone effect
–	+	28	54	0.97 (0.56,1.70); 0.924	E alone effect
–	–	57	107	1.00 (reference)	Common control
GA vs GG	Smoking
+	+	35	43	1.53 (0.88,2.65); 0.130	G, E combined effect
+	–	67	93	1.35 (0.86,2.12); 0.187	G alone effect
–	+	28	54	0.97 (0.56,1.70); 0.924	E alone effect
–	–	57	107	1.00 (reference)	Common control
AA vs GG	Drinking
+	+	8	7	2.14 (0.74,6.17); 0.153	G, E combined effect
+	–	22	22	1.87 (0.96,3.64); 0.064	G alone effect
–	+	24	47	0.95 (0.53,1.71); 0.875	E alone effect
–	–	61	114	1.00 (reference)	Common control
GA vs GG	Drinking
+	+	36	45	1.50 (0.87,2.56); 0.141	G, E combined effect
+	–	66	91	1.36 (0.87,2.11); 0.179	G alone effect
–	+	24	47	0.95 (0.53,1.71); 0.875	E alone effect
–	–	61	114	1.00 (reference)	Common control
rs763780
CC vs TT	Smoking
+	+	10	6	2.85 (1.00,8.13); 0.042	G, E combined effect
+	–	4	6	1.61 (0.58,4.47); 0.359	G alone effect
–	+	37	71	0.89 (0.55,1.44); 0.640	E alone effect
–	–	83	142	1.00 (reference)	Common control
TC vs TT	Smoking
+	+	28	28	1.71 (0.95,3.09); 0.073	G, E combined effect
+	–	55	73	1.29 (0.83,2.01); 0.260	G alone effect
–	+	37	71	0.89 (0.55,1.44); 0.640	E alone effect
–	–	83	142	1.00 (reference)	Common control
CC vs TT	Drinking
+	+	6	5	2.16 (0.64,7.31); 0.205	G, E combined effect
+	–	8	7	2.06 (0.72,5.89); 0.170	G alone effect
–	+	39	67	1.05 (0.65,1.69); 0.844	E alone effect
–	–	81	146	1.00 (reference)	Common control
TC vs TT	Drinking
+	+	23	27	1.54 (0.83,2.85); 0.173	G, E combined effect
+	–	60	74	1.46 (0.95,2.26); 0.087	G alone effect
–	+	39	67	1.05 (0.65,1.69); 0.844	E alone effect
–	–	81	146	1.00 (reference)	Common control

Notes: ^aG (+): IL-23R gene rs11209026 and IL-17 gene rs36084323/rs7421861 polymorphisms (heterozygous or homozygous); G (-): wild type; ^bE(+): smoking/non-smoking; E(-): non-smoking/non-drinking. Bold values are statistically significant (P < 0.05).

Figure 1 ROC curve for IL-23 and IL-17 serum levels to predict the occurrence of RVVC.

Table 5 Predictive Values of IL-17 and IL-23 Serum Levels in Detecting Recurrent Vulvovaginal Candidiasis

	Youden Index J	Associated Criterion	Sensitivity	Specificity	AUC*	95% CI	P-value
IL-23	0.306	>28.67	73.91%	56.73%	0.653	(0.58–0.71)	<0.0001
IL-17	0.409	>5.98	69.57%	71.35%	0.755	(0.69–0.81)	<0.0001

Notes: *AUC, area under the ROC curve; Bold values are statistically significant (P < 0.05).