STAT6 rs324015 Gene Polymorphism Increases Ulcerative Colitis Risk: A Case–Control Study

Figures & data

Table 1 Demographics of Study Participants

Characteristics	Case (N=268)	Control (N=357)	P
Age	35.57±8.60	35.80±9.61	0.759
BMI	24.40±1.55	24.27±1.47	0.290
Sex			0.234
Male	132(49.3%)	193(54.1%)
Female	136(50.7%)	164(45.9%)
Smoking			<0.001
Yes	144(53.7%)	138(38.7%)
No	124(46.3%)	219(61.3%)
Alcohol			0.154
Yes	101(37.7%)	115(32.2%)
No	167(62.3%)	242(67.8%)
Family history
Yes	25(9.3%)
No	243(90.7%)
Lesion location of UC
Distal colitis(E1+E2)	168(62.7%)
Extensive colitis(E3)	100(37.3%)
Severity of UC
Mild	111(41.4%)
Intermediate	125(46.6%)
Severe	32(11.9%)

Note: Bold values are stitistically significant (P < 0.05).Abbreviations: BMI, body mass index; UC, ulcerative colitis.

Table 2 The Association of Genotype and Allele of the STAT6 rs324015 Polymorphism with Ulcerative Colitis Risk

Models	Genotype	Case (n, %)	Control (n, %)	OR (95% CI)	P-value	*OR (95% CI)	*P-value
Co-dominant	AA	126(47.2%)	200(56.3%)	1.00(reference)	-	1.00(reference)	-
Heterozygote	AG	115(43.1%)	133(37.5%)	1.37(0.98-1.92)	0.064	1.40(1.00-1.96)	0.050
Homozygote	GG	26(9.7%)	22(6.2%)	1.88(1.02-3.45)	0.043	1.92(1.04-3.54)	0.037
Dominant	AA	126(47.2%)	200(56.3%)	1.00(reference)	-	1.00(reference)	-
	GG+AG	141(52.8%)	155(43.7%)	1.44(1.05-1.99)	0.024	1.48(1.07-2.04)	0.018
Recessive	AG+AA	241(90.3%)	333(93.8%)	1.00(reference)	-	1.00(reference)	-
	GG	26(9.7%)	22(6.2%)	1.63(0.90-2.95)	0.104	1.66(0.92-3.00)	0.095
Allele	A	367(68.7%)	533(75.1%)	1.00(reference)	-	1.00(reference)	-
	G	167(31.3%)	177(24.9%)	1.37(1.07-1.76)	0.013	-	-

Notes: The genotyping was successful in 267 cases and 355 controls for rs324015 polymorphism; Bold values are statistically significant (P < 0.05); *Adjust age and sex.

Table 3 Stratified Analyses Between the STAT6 rs324015 Polymorphism and the Risk of Ulcerative Colitis

Variables	(Case/Control)			AG vs AA	GG vs AA	GG vs AG+AA	GG+AG vs AA
	AA	AG	GG
Sex
Male	55/99	63/78	13/14	1.45(0.91-2.32); 0.116	1.67(0.73-3.81); 0.218	1.39(0.63-3.07); 0.409	1.49(0.95-2.33); 0.082
Female	71/101	52/55	13/8	1.35(0.83-2.19); 0.231	2.31(0.91-5.87); 0.072	2.06(0.83-5.13); 0.114	1.47(0.93-2.33); 0.102
Smoking
Yes	56/72	71/54	17/10	1.69(1.03-2.78); 0.038	2.19(0.93-5.14); 0.073	1.69(0.74-3.83); 0.207	1.77(1.10-2.84); 0.018
No	70/128	44/79	9/12	1.02(0.64-1.63); 0.939	1.37(0.55-3.41); 0.496	1.36(0.56-3.33); 0.497	1.07(0.68-1.67); 0.782
Alcohol
Yes	29/66	60/42	12/7	3.25(1.81-5.86); <0.001	3.90(1.39-10.92); 0.007	2.08(0.79-5.51); 0.134	3.34(1.90-5.90); <0.001
No	97/134	55/91	14/15	0.84(0.55-1.28); 0.405	1.29(0.60-2.80); 0.519	1.38(0.65-2.95); 0.401	0.90(0.60-1.34); 0.603
Age (years)
<40	84/96	101/66	21/10	1.75(1.14-2.68); 0.010	2.40(1.07-5.38); 0.030	1.84(0.84-4.02); 0.122	1.84(1.22-2.76); 0.004
≥40	42/104	14/67	5/12	0.52(0.26-1.02); 0.055	1.03(0.34-3.11); 1.000	1.27(0.43-3.77); 0.885	0.60(0.32-1.10); 0.097

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
GG vs AA	Smoking
+	+	17	10	3.11(1.35,7.16); 0.006	G, E combined effect
+	-	9	12	1.37(0.55,3.41); 0.496	G alone effect
-	+	56	72	1.42(0.90,2.24); 0.128	E alone effect
-	-	70	128	1.0	Common control
AG vs AA	Smoking
+	+	71	54	2.40(1.52,3.80); <0.001	G, E combined effect
+	-	44	79	1.02(0.64,1.63); 0.939	G alone effect
-	+	56	72	1.42(0.90,2.24); 0.128	E alone effect
-	-	70	128	1.0	Common control
GG vs AA	Drinking
+	+	12	7	2.37(0.90,6.24); 0.074	G, E combined effect
+	-	14	15	1.29(0.60,2.80); 0.519	G alone effect
-	+	29	66	0.61(0.37,1.01); 0.053	E alone effect
-	-	97	134	1.0	Common control
AG vs AA	Drinking
+	+	60	42	1.97(1.23,3.17); 0.005	G, E combined effect
+	-	55	91	0.84(0.55,1.28); 0.405	G alone effect
-	+	29	66	0.61(0.37,1.01); 0.053	E alone effect
-	-	97	134	1.0	Common control

Notes: ^aG (+): STAT6 gene rs324015 variants (Heterozygous or homozygous); G (-): Wild type. ^bE (+): Smoking/drinking; E (-): Non-smoking/non-drinking. Bold values are statistically significant (P < 0.05).

Table 5 The Association Between the STAT6 rs324015 Polymorphism and Clinical Characteristics of Ulcerative Colitis

Characteristics	Genotype Distributions
	AA	AG	GG	AG+GG
Family history
Yes/No	11/115	9/106	5/21	14/127
OR (95%CI); P-value	1.0 (reference)	0.89(0.35-2.23); 0.799	2.49(0.78-7.90); 0.112	1.15(0.50-2.64); 0.737
Lesion location of UC
E3/E1+E2	37/89	50/65	13/13	63/78
OR (95%CI); P-value	1.0 (reference)	1.85(1.09-3.15); 0.023	2.41(1.02-5.68); 0.041	1.94(1.17-3.23); 0.010
Severity of UC
Severe/mild	7/58	20/43	5/10	25/53
OR (95%CI); P-value	1.0 (reference)	3.85(1.50-9.93); 0.004	4.14(1.10-15.66); 0.071	3.91(1.56-9.78); 0.002
Severity of UC
Severe/intermediate	7/61	20/52	5/11	25/63
OR (95%CI); P-value	1.0 (reference)	3.35(1.31-8.55); 0.009	3.96(1.06-14.75); 0.079	3.46(1.39-8.58); 0.005

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

Figure 1 The relative STAT6 mRNA expression among three genotypes of rs324015 polymorphism (*P < 0.05, GG genotype vs AA genotype).