Genetic associations of inflammatory bowel disease in a South Asian population

Table 1 Characteristics of the patient population, n (%)

Characteristic	CD (n = 153)	UC (n = 258)	P1
Male gender	77 (50.3)	123 (47.7)	0.80
Age in years (mean, SD)	41.0 (16.9)	47.6 (14.9)	< 0.01
Race
Sinhala	129 (84.31)	229 (88.75)
Tamil	11 (7.19)	13 (5.06)
Muslim	11 (7.19)	13 (5.03)
Other	2 (1.31)	3 (1.17)
Body mass index mg/m2 (mean, SD)	21.4 (4.6)	22.9 (4.5)	< 0.01
Family history of IBD	7 (4.6)	12 (4.7)	0.98
Comorbidities
Diabetes	11 (7.1)	41 (15.9)	0.01
Hypertension	16 (10.5)	37 (14.3)	0.26
BA/COPD	9 (5.8)	22 (8.5)	0.33
Tuberculosis	7 (4.6)	1 (0.4)	< 0.01
Tobacco smoking	25 (16.3)	49 (18.9)	0.39
Disease characteristics
Duration of the disease (yr)	4.8 (4.2)	7.3 (5.7)	< 0.01
Extensive disease in UC	76 (29.5)	-	-
Upper GI disease in CD	11 (7.2)	-	-
Severe/complicated disease	47 (30.7)	130 (50.4)	< 0.01
Maintained remission	142 (92.9)	245 (95.0)	0.83
Treatment refractory disease	24 (15.68)	24 (9.3)	< 0.05
Use of biologics	16 (10.5)	7 (2.7)	< 0.01

¹Unadjusted univariate P value. IBD: Inflammatory bowel disease; CD: Crohn's disease; UC: Ulcerative colitis; GI: Gastrointestinal; BA: Bronchial asthma; COPD: Chronic obstructive pulmonary disease.

Table 2 Results of the case’s control analysis for the association of single nucleotide polymorphisms with inflammatory bowel disease

SNPs	Variant allele	Genotypes	Controls (465), n (%)	Cases (415), n (%)	Odds ratio1	95%CI		P
rs10045431	C	AA	5 (1.08)	5 (1.2)
		CA	114 (24.52)	83 (20)	0.77	0.56	1.06	0.11
		CC	346 (74.41)	327 (78.8)	1.06	0.30	3.69	0.93
rs11805303	T	CC	93 (20)	53 (12.77)
		TC	236 (50.75)	207 (49.88)	1.54	1.05	2.26	0.03
		TT	136 (29.25)	155 (37.35)	2.00	1.33	3.01	0.00
rs12612347	G	AA	67 (14.41)	69 (16.63)
		GA	229 (49.25)	191 (46.02)	0.81	0.55	1.19	0.29
		GG	169 (36.34)	155 (37.35)	0.89	0.60	1.33	0.57
rs13361189	C	TT	267 (57.42)	235 (56.63)
		CT	172 (36.99)	153 (36.87)	1.01	0.76	1.34	0.94
		CC	26 (5.59)	27 (6.51)	1.18	0.67	2.08	0.57
rs1558744	A	GG	347 (74.62)	289 (69.64)
		AG	116 (24.95)	118 (28.43)	1.22	0.90	1.65	0.19
		AA	2 (0.43)	8 (1.93)	4.80	1.01	22.79	0.04
rs1728785	A	CC	261 (56.13)	253 (60.96)
		CA	184 (39.57)	139 (33.49)	0.78	0.59	1.03	0.08
		AA	20 (4.3)	23 (5.54)	1.19	0.64	2.21	0.59
rs3024505	A	GG	373 (80.22)	322 (77.59)
		GA	89 (19.14)	89 (21.45)	1.16	0.83	1.61	0.38
		AA	3 (0.65)	4 (0.96)	1.54	0.34	6.95	0.57
rs3737240	T	CC	262 (56.34)	215 (51.81)
		TC	172 (36.99)	167 (40.24)	1.18	0.90	1.56	0.24
		TT	31 (6.67)	33 (7.95)	1.30	0.77	2.19	0.33
rs4613763	C	TT	461 (99.14)	408 (98.31)	1.98	0.57	6.80	0.28
		CT	4 (0.86)	7 (1.69)	0.89	0.77	1.01	0.07
		CC	0 (0)	0 (0)
rs5771069	A	GG	264 (56.77)	248 (59.76)
		GA	160 (34.41)	144 (34.7)	0.96	0.72	1.27	0.77
		AA	41 (8.82)	23 (5.54)	0.60	0.35	1.02	0.06
rs6017342	A	CC	217 (46.67)	223 (53.73)
		CA	200 (43.01)	154 (37.11)	0.75	0.57	0.99	0.04
		AA	48 (10.32)	38 (9.16)	0.77	0.48	1.23	0.27
rs744166	G	AA	86 (18.49)	100 (24.1)
		AG	238 (51.18)	203 (48.92)	0.73	0.52	1.03	0.08
		GG	141 (30.32)	112 (26.99)	0.68	0.47	1.00	0.05
rs7809799	G	AA	405 (87.1)	361 (86.99)
		GA	58 (12.47)	50 (12.05)	0.97	0.65	1.45	0.87
		GG	2 (0.43)	4 (0.96)	2.24	0.41	12.32	0.35
rs886774	G	AA	154 (33.12)	104 (25.06)
		GA	214 (46.02)	199 (47.95)	1.38	1.01	1.89	0.05
		GG	97 (20.86)	112 (26.99)	1.71	1.18	2.47	0.00
rs9268853	C	TT	210 (45.16)	203 (48.92)
		CT	208 (44.73)	164 (39.52)	0.82	0.62	1.08	0.16
		CC	47 (10.11)	48 (11.57)	1.06	0.68	1.65	0.81
rs9822268	A	GG	284 (61.08)	280 (67.47)
		GA	163 (35.05)	117 (28.19)	0.73	0.55	0.97	0.03
		AA	18 (3.87)	18 (4.34)	1.01	0.52	1.99	0.97

¹Reports the odds of being a case for heterozygous and homozygous individuals with the recessive allele compared to the controls. SNPs: Single nucleotide polymorphisms.

Table 3 Associations of variants with Crohn’s disease and ulcerative colitis

SNPs	Candidate gene	Associated subtype	Heterogenous		Homogenous
			odds ratio1	P	odds ratio1	P
rs10045431	IL 12B	CD	0.579	0.027	2.491	0.178
rs11805303	IL23R	CD	0.909	0.609	1.505	0.010
rs12612347	ARPC2	UC	0.896	0.479	0.991	0.957
rs13361189	IRGM	CD	1.093	0.578	1.355	0.331
rs1558744	IFN-c, IL26, IL22	UC	1.043	0.811	5.560	0.036
rs1728785	CDH1	UC	0.829	0.244	1.410	0.314
rs3024505	IL10	UC	1.194	0.351	2.446	0.244
rs3737240	FCGR2A	UC	1.182	0.291	1.187	0.564
rs4613763	PTGER4	CD	2.325	0.273	2	-
rs5771069	IL17REL/PIM3	UC	0.915	0.589	0.599	0.109
rs6017342	HNF4a, SERINC3	UC	0.690	0.021	0.920	0.746
rs744166	STAT3	CD	0.841	0.266	0.900	0.541
rs7809799	SMURF1	UC	1.149	0.542	2.747	0.270
rs8867743	LAMB1	UC	1.163	0.330	1.494	0.001
rs9268853	HLA DRB5	UC	0.684	0.017	1.049	0.850
rs9822268	APEH	UC	0.748	0.748	1.116	0.779

¹Odds ratios when comparing patients with healthy controls;

²No heterozygous individuals were present in this study population;

³Significantly associated with the relevant phenotype after Bonferroni correction. SNPs: Single nucleotide polymorphisms; CD: Crohn’s disease; UC: Ulcerative colitis.

Table 4 Association of single nucleotide polymorphisms with clinical characteristics of ulcerative colitis and Crohn’s disease

Characteristic	SNPs	OR1	P	95%CI
Risk for UC	rs11805303	1.35	0.009	1.08	1.69
Extensive disease in UC	rs9268853	0.59	0.009	0.37	0.82
Upper GI disease in CD	rs10045431	4.42	0.002	1.75	12.92
Mild disease in UC	rs886774	1.66	< 0.001	1.13	2.17
Maintained UC remission	rs886774	1.48	< 0.001	1.19	1.85
Use of biologics in CD	rs9268853	3.36	0.004	1.48	7.58

¹Univariate odds for the presence of single nucleotide polymorphisms in patients with characteristics tested against healthy controls. OR: Odds ratio; SNPs: Single nucleotide polymorphisms; GI: Gastrointestinal; CD: Crohn’s disease; UC: Ulcerative colitis.