Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

doi:10.3748/wjg.v20.i1.219

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 7, 2014; 20(1): 219-227
Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.219

Table 1 Primer sequences for the analysed variants

Gene	SNP	Primers (5’-3’)
IL23R	rs1004819	Forward: GCATTCTAGGACCGTTTTGG
IL23R	rs1004819	Reverse: ATCTGGTGGAAATATGTGAAACCTA
IL23R	rs2201841	Forward: GGCAAAAGGGAATTGAGAGG
IL23R	rs2201841	Reverse: GGCCTATGATTATGCTTTTTCCTG¹
SLC22A4	rs1050152	Forward: AGAGAGTCCTCCTATCTGATTG
SLC22A4	rs1050152	Reverse: TCCTAGCTATTCTTCCATGC
SLC22A5	rs2631367	Forward: GCCGCTCTGCCTGCCAGC
SLC22A5	rs2631367	Reverse: GGTCGCTATCAGGAACACGGAGGA
IGR2230a_1	rs17622208	Forward: CAGAAGAATGCCCTTGATGTG
IGR2230a_1	rs17622208	Reverse: TCAGAAGCTGTCCATCCCAC
IGR2198a_1	rs11739135	Forward: AGACACTGGGACATCATCTGTCTG
IGR2198a_1	rs11739135	Reverse: GGGCAATTCTATGAGGACATTTAGA
IGR2096a_1	rs12521868	Forward: CAAGATTTCTGCCATAGCCTCCT
IGR2096a_1	rs12521868	Reverse: GGAGGGTGGTGTAGCCAGAGTAG

¹Mismatch base is underlined.

Table 2 Case-control genotypes and allele frequencies of variants in IL23R and inflammatory bowel disease-5 locus n (%)

	UC (n = 320)	Controls (n = 316)	OR (95%CI)¹	P value
IL23R (rs1004819)
GG	126 (39.4)	158 (50.0)
GA	168 (52.5)	134 (42.4)
GA + AA	194 (60.6)	158 (50.0)	1.606 (1.160-2.223)^a	0.004^a
AA	26 (8.1)	24 (7.6)	1.254 (0.696-2.261)	0.452
RAF	0.343	0.287		0.032^a
IL23R (rs2201841)
TT	140 (43.8)	155 (49.1)
TC	150 (46.9)	143 (45.3)
TC + CC	180 (56.3)	161 (51.0)	1.268 (0.920-1.749)	0.147
CC	30 (9.4)	18 (5.7)	1.983 (1.069-3.678)^a	0.030^a
RAF	0.328	0.283		0.242
SLC22A4 (rs1050152)
CC	93 (29.1)	110 (34.8)
CT	159 (49.7)	148 (46.8)
CT + TT	227 (71.0)	206 (65.2)	1.319 (0.935-1.86)	0.115
TT	68 (21.3)	58 (18.4)	1.150 (0.768-1.723)	0.498
RAF	0.46	0.417		0.120
SLC22A5 (rs2631367)
GG	83 (25.9)	89 (28.2)
GC	163 (50.9)	156 (49.4)
GC + CC	237 (74.0)	227 (71.9)	1.138 (0.794-1.631)	0.481
CC	74 (23.1)	71 (22.5)	0.982 (0.669-1.440)	0.925
RAF	0.485	0.471		0.607
IGR2230a_1 (rs17622208)
GG	87 (27.2)	90 (28.5)
AG	160 (50.0)	157 (49.7)
AG + AA	233 (72.8)	226 (71.5)	1.073 (0.751-1.532)	0.698
AA	73 (22.8)	69 (21.8)	0.990 (0.673-1.457)	0.960
RAF	0.478	0.466		0.685
IGR2198a_1 (rs11739135)
GG	105 (32.8)	117 (37.0)
GC	159 (49.7)	150 (47.5)
GC + CC	215 (67.2)	199 (63.0)	1.260 (0.900-1.763)	0.179
CC	56 (17.5)	49 (15.5)	1.169 (0.760-1.797)	0.477
RAF	0.423	0.392		0.260
IGR2096a_1 (rs12521868)
GG	101 (31.6)	117 (37.0)
GT	164 (51.3)	147 (46.5)
GT + TT	219 (68.5)	199 (63.0)	1.256 (0.897-1.760)	0.185
TT	55 (17.2)	52 (16.5)	1.045 (0.680-1.608)	0.840
RAF	0.428	0.397		0.262

¹Adjusted for age and gender.

^aAssociations significant at P < 0.05 vs controls. RAF: Risk allele frequency; UC: Ulcerative colitis.

Table 3 Pairwise analysis of interactions of IBD5 and IL23R to risk of ulcerative colitis

Model	OR (95%CI)	P value
IL23R rs1004819 * IGR2230a_1	1.266 (0.627-2.553)	0.51
IL23R rs1004819 * IGR2198a_1	1.383 (0.711-2.690)	0.340
IL23R rs1004819 * IGR2096a_1	0.942 (0.625-1.420)	0.776
IL23R rs1004819 * SLC22A4	1.017 (0.516-2.002)	0.962
IL23R rs1004819 * SLC22A5	1.116 (0.549-2.270)	0.761
IL23R rs2201841 Ho* IGR2230a_1	0.316 (0.080-1.247)	0.100
IL23R rs2201841 Ho* IGR2198a_1	0.388 (0.105-1.430)	0.155
IL23R rs2201841 Ho* IGR2096a_1	0.413 (0.117-1.458)	0.169
IL23R rs2201841 Ho* SLC22A4	0.118 (0.095-1.301)	0.352
IL23R rs2201841 Ho* SLC22A5	0.298 (0.075-1.179)	0.084

Ho: Homozygotes.

Table 4 Genotype-specific ulcerative colitis odds ratios (with 95%CI) for combinations of variants in IL23R and IBD5

	SLC22A4		SLC22A5		IGR2230a_1		IGR2198a_1		IGR2096a_1
	CC	CT + TT	GG	GC + CC	GG	AG + AA	GG	GC + CC	GG	GT + TT
IL23R rs1004819
GG	1	1.298	1	1.064	1	0.941	1	1.033	1	1.104
		(0.782-2.156)		(0.623-1.815)		(0.556-1.593)		(0.623-1.711)		(0.666-1.831)
		P = 0.313		P = 0.821		P = 0.822		P = 0.900		P = 0.702
GA + AA	1.527	¹2.015	1.424	¹1.691	1.300	1.549	1.263	¹1.803	1.281	¹1.911
	(0.872-2.673)	(1.230-3.300)	(0.776-2.614)	(1.003-2.821)	(0.716-2.359)	(0.927-2.588)	(0.736-2.166)	(1.096-2.966)	(0.744-2.206)	(1.162-3.143)
	P = 0.138	P = 0.005	P = 0.253	P = 0.048	P = 0.388	P = 0.093	P = 0.396	P = 0.020	P = 0.372	P = 0.010
IL23R rs2201841
TT+TC	1	1.328	1	1.254	1	1.184	1	1.296	1	1.385
		(0.989-1.927)		(0.868-1.812		(0.823-1.704)		(0.922-1.822)		(0.982-1.953)
		P = 0.058		P = 0.228		P = 0.363		P = 0.136		P = 0.063
CC	¹3.413	1.716	¹3.946	1.474	¹3.777	1.411	¹3.165	1.592	¹2.977	¹1.701
	(1.169-9.965)	(0.788-3.739	(1.232-12.645)	(0.679-3.200)	(1.181-12.084)	(0.652-3.056)	(1.088-9.206)	(0.735-3.449)	(1.099-8.066)	(0.765-3.784)
	P = 0.018	P = 0.171	P = 0.014	P = 0.324	P = 0.018	P = 0.381	P = 0.027	P = 0.236	P = 0.026	P = 0.189

¹Associations significant at P < 0.05 vs controls.

Citation: Sarlos P, Varszegi D, Csongei V, Magyari L, Jaromi L, Nagy L, Melegh B. Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions. World J Gastroenterol 2014; 20(1): 219-227
URL: https://www.wjgnet.com/1007-9327/full/v20/i1/219.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i1.219