Multidrug resistance 1 gene in inflammatory bowel disease: A meta-analysis

Table 1 Substrates (S), inhibitors (I-) and inducers (I+) of P-glycoprotein (Modified from ref. 9)

DRUG	S	I-	I+	DRUG	S	I-	I+
Anticancer				Antiviral
Actinomycin D	√			Amprenavir	√		√
Daunorubicin	√			Indinavir	√	√	√
Mitomicyn C	√			Nelfinavir	√	√	√
Mitoxantrone	√			Antibiotics
Vinblastine	√			Claritromycin		√
Vincristine	√			Erythromycin	√	√
Antihypertensive				Levofloxacin	√
Diltiazem	√			Rifampin	√		√
Losartan	√			Tetracycline	√
Nicardipine		√		Antimycotics
Talinolol	±			Itraconazole	√	√
Antiarrhythmics				Ketoconazole		√
Amiodarone		√		Immunosup.
Digoxin	√			Cyclosporine	√	√
Quinidine	√	√		Tacrolimus	√	√
Verapamil	√	√		Methotrexate	√
Glucocorticoids				Antidepressants
Aldosterone	√			Amitriptyline	√
Cortisol	√			Fluoxetine		√
Dexamethasone	√		√	Neuroleptics
Methylprednisolone	√			Chlorpromazine		√
Others				Phenotiazine		√
Colchicine	√			Phenobarbital	√
Dipyridamole		√		Opioids
Loperamide	√			Methadone		√
Progesterone		√		Morphine	√
Spironolactone		√		Antacids
Domperidone	√			Ranitidine	√
Ondansetron	√			Cimetidine	√

Table 2 Distribution of C3435T alleles and genotypes (cases and controls) in the existing literature

	C	T	CC	CT	TT
Glas, 2003
UC = 1231	111 (45)	135 (55)	19 (15)	73 (60)	31 (25)
CD = 135	130 (48)	140 (52)	26 (19)	78 (58)	31 (23)
IBD = 258	241 (47)	275 (53)	45 (17)	151 (59)	62 (24)
HC = 265	272 (51)	258 (49)	70 (26)	132 (50)	63 (24)
Schwab, 2003	C	T	CC	CT	TT
UCa = 149	129 (43)	169 (57)	26 (17)	77 (52)	46 (31)
HC = 149	154 (52)	144 (48)	39 (26)	76 (51)	34 (23)
CD = 126	134 (53)	118 (47)	33 (26)	68 (54)	25 (20)
HC = 126	128 (51)	124 (49)	35 (28)	58 (46)	33 (26)
IBD = 275	263 (48)	287 (52)	59 (21)	145 (53)	71 (26)
HC = 275	282 (51)	268 (49)	74 (27)	134 (49)	67 (24)
Ho, 2005	C	T	CC	CT	TT
UCc = 335	280 (42)	390 (58)	61 (18)	158 (47)	116 (35)
CD = 268	252 (47)	284 (53)	56 (21)	140 (52)	72 (27)
IBD = 603	532 (44)	674 (56)	117 (19)	298 (50)	188 (31)
HC = 370	354 (48)	386 (52)	82 (22)	190 (51)	98 (27)
Palmieri, 2005	C	T	CC	CT	TT
UC = 468	488 (52)	448 (48)	124 (27)	240 (51)	104 (22)
CD = 478	503 (53)	453 (47)	125 (26)	253 (53)	100 (21)
IBD = 946	991 (52)	901 (48)	249 (26)	493 (52)	204 (22)
HC = 450	470 (52)	430 (48)	115 (26)	240 (53)	95 (21)
Potocnik, 2004	C	T	CC	CT	TT
UC = 144	134 (47)	154 (53)	-	-	-
CD = 163	161 (49)	165 (51)	-	-	-
IBD = 307	295 (48)	319 (52)
HC = 355	376 (53)	334 (47)	-	-	-
Urcelay, 2006
UC = 311	317 (51)	305 (49)	87 (28)	143 (46)	81 (26)
CDb = 3031	369 (61)	237 (39)	122 (40)	125 (41)	56 (19)
IBD = 614	686 (56)	542 (44)	209 (34)	268 (44)	137 (22)
HC = 324	344 (53)	304 (47)	97 (30)	150 (46)	77 (24)

UC = Ulcerative colitis, CD = Crohn’s disease, HC = healthy controls. ^aP = 0.045 (T vs C); P = 0.049 (TT vs CC). ^cP = 0.02 (T vs C); P = 0.04 (TT vs CC). ^bP = 0.006 (T vs C); P = 0.01 (TT vs CC). ¹ Subjects not in Hardy-Weinberg equilibrium.

Table 3 Distribution of G2677T/A alleles and genotypes (cases and controls) in the existing literature

	A	G	T	AA	GG	GT	TT	GA	TA
Brant, 2003
IBD_NJa = 211	2 (0.5)	254 (60.2)	166 (39.3)	-	76 (36)	101 (48)	32 (15)	1 (0.5)	1 (0.5)
HC_NJ = 392	20 (2.6)	411 (52.4)	353 (45)	-	108 (27)	183 (47)	81 (21)	12 (3)	8 (2)
IBD_J = 114	1 (0.5)	143 (62.7)	84 (36.8)	-	41 (36)	60 (53)	12 (10)	1 (1)	0
HC_J = 219	13 (3)	265 (60.5)	160 (36.5)	-	85 (39)	89 (41)	32 (15)	6 (2)	7 (3)
Ho, 2005	A	G	T	AA	GG	GT	TT	GA	TA
UC = 335	-	366 (54.6)	304 (45.4)	-	95 (28.3)	176 (52.5)	64 (19.1)	-	-
CD = 268	-	283 (52.8)	253 (47.2)	-	75 (27.9)	133 (47.8)	60 (22.4)	-	-
IBD = 603	-	649 (53.8)	557 (46.2)	-	170 (28.2)	309 (51.2)	124 (20.6)	-	-
HC = 370	-	378 (51.2)	362 (49.8)	-	102 (27.6)	174 (47.0)	94 (25.4)	-	-
Palmieri, 2005	A	G	T	AA	GG	GT	TT	GA	TA
UC = 468	23 (2.5)	494 (52.8)	419 (44.7)	1 (0.2)	127 (27.1)	229 (49.0)	90 (19.2)	11 (2.4)	10 (2.1)
CD = 478	15 (1.6)	534 (55.9)	407 (42.5)	0 (0.0)	143 (29.9)	237 (49.6)	83 (17.4)	11 (2.3)	4 (0.8)
IBD = 946	38 (2)	1028 (54)	826 (44)	1 (0.1)	270 (29.5)	466 (49.2)	173 (18.3)	22 (2.3)	14 (1.5)
HC = 450	19 (2.1)	500 (55.6)	381 (42.3)	0 (0.0)	126 (28.0)	236 (52.4)	69 (15.3)	12 (2.7)	7 (1.6)
Potocnik, 2004		A & G	T
UC = 144	-	157 (54)	131 (46)	-	-	-	-	-	-
CD = 163	-	187 (57)	139 (43)	-	-	-	-	-	-
IBD = 307	-	344 (56)	270 (44)	-	-	-	-	-	-
HC = 355	-	424 (59.7)	286 (40.3)	-	-	-	-	-	-
Urcelay, 2006
UC = 311	4 (0.7)	372 (62.8)	216 (36.5)	0 (0)	118 (39.9)	133 (44.9)	41 (13.9)	3 (1)	1 (0.3)
CD = 303	6 (0.9)	403 (63.2)	229 (35.9)	0 (0)	139 (43.6)	122 (38.3)	52 (16.3)	3 (0.9)	3 (0.9)
IBD = 615	10 (0.8)	775 (63)	445 (36.2)	0 (0)	257 (41.8)	255 (41.5)	93 (16.1)	6 (0.9)	4 (0.7)
HC = 352	8 (1.1)	426 (60.5)	270 (38.4)	0 (0)	140 (39.8)	142 (40.3)	62 (17.6)	4 (1.1)	4 (1.1)

^aP = 0.03 (G vs T); P = 0.08 (GG vs GT TT).

Table 4 Summary of ORs and 95% CIs for different outcomes obtained at the meta-analysis

		Fixed effects		Random effects		Heterogeneity test
		P value	OR (95% CI)	P value	OR (95% CI)
C3435T	Outcome CD T vs C (6 studies)	0.519	0.968 (0.878-1.068)	0.722	0.974 (0.842-1.126)	0.09
	TT vs CC (5 studies)	0.297	0.892 (0.720-1.106)	0.472	0.900 (0.675-1.200)	NS
G2677T/A	G vs T (4 studies)	0.635	1.027 (0.920-1.145)	0.635	1.027 (0.920-1.145)	NS
	GG vs GT TT (3 studies) Outcome UC	0.338	1.092 (0.912-1.308)	0.338	1.092 (0.912-1.308)	NS
C3435T	T vs C (6 studies)	0.002	1.170 (1.062-1.289)	0.003	1.178 (1.058-1.311)	NS
	TT vs CC (5 studies)	0.008	1.332 (1.080-1.644)	0.017	1.367 (1.057-1.768)	NS
G2677T/A	G vs T (4 studies)	0.843	0.989 (0.887-1.103)	0.862	0.986 (0.836-1.162)	NS
	GG vs GT TT (3 studies) Outcome IBD	0.947	0.994 (0.830-1.190)	0.947	0.994 (0.830-1.190)	NS
C3435T	T vs C (6 studies)	0.083	1.074 (0.991-1.165)	0.135	1.083 (0.976-1.201)	NS
	TT vs CC (5 studies)	0.225	1.116 (0.935-1.332)	0.274	1.135 (0.904-1.426)	NS
G2677T/A	G vs T (5 studies)	0.351	1.041 (0.957-1.132)	0.448	1.047 (0.930-1.178)	NS
	GG vs GT TT (4 studies)	0.366	1.065 (0.929-1.221)	0.366	1.065 (0.929-1.221)	NS