Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response and pharmacokinetics in a Japanese population

Hashiguchi, Masayuki; Shimizu, Mikiko; Hakamata, Jun; Tsuru, Tomomi; Tanaka, Takanori; Suzaki, Midori; Miyawaki, Kumika; Chiyoda, Takeshi; Takeuchi, Osamu; Hiratsuka, Jiro; Irie, Shin; Maruyama, Junya; Mochizuki, Mayumi

doi:10.1186/s40780-016-0069-0

Journal of Pharmaceutical Health Care and Sciences

Table 2 Comparison of distribution of MTX-related enzyme gene and transporter polymorphisms among ethnic or population group in the patients with rheumatoid arthritis

From: Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response and pharmacokinetics in a Japanese population

Ethnic/Population group	n	Genotype frequency (n)			HWE	Allele frequency (%)		p-value	Reference No.
MTHFR 1298		A/A	A/C	C/C		A	C
Japanese (Our study)	159	109 (68.6)	42 (26.4)	8 (5.0)	0.149	82	18
Japanese	357	232 (65.0)	107 (30.0)	18 (5.0)	0.224	80	20	0.7070	[5, 6, 20, 21]
Chinese	93	63 (67.7)	29 (31.2)	1 (1.1)	0.237	83	27	0.1690	[22]
Caucasian	1828	809 (44.3)	785 (42.9)	234 (12.8)	0.045	66	34	p<0.0001	[23–31]
African-American	138	102 (74.0)	35 (25.0)	1 (1.0)	0.278	87	13	0.0614	[26]
TYMS 3'-UTR		−6/−6	−6/+6	+6/+6		−6	+6
Japanese (Our study)	159	72 (45.3)	67 (42.1)	20 (12.6)	0.477	66	34
Japanese	409	173 (42.3)	193 (47.2)	43 (10.5)	0.314	66	34	0.5180	[6, 9, 32]
Caucasian	98	10 (10.2)	37 (37.8)	51 (52.0)	0.053	29	71	< 0.0001	[24]
RFC1 80		G/G	G/A	A/A		G	A
Japanese (Our study)	159	34 (21.4)	74 (46.5)	51 (32.1)	0.461	45	55
Japanese	681	135 (19.8)	348 (51.1)	198 (29.1)	0.421	45	55	0.5820	[5, 9, 20, 21, 32, 33]
Caucasian	611	187 (30.6)	275 (45.0)	149 (24.4)	0.017	53	47	0.0360	[24, 34–36]
RFC1−43		T/T	T/C	C/C		T	C
Japanese (Our study)	159	34 (21.4)	74 (46.5)	51 (32.1)	0.461	45	55
Caucasian	106	39 (36.8)	47 (44.3)	20 (18.9)	0.388	59	41	0.0760	[34]
FPGS 1994		G/G	G/A	A/A		G	A
Japanese (Our study)	159	70 (44.0)	73 (45.9)	16 (10.1)	0.632	67	33
Caucasian	205	42 (21.0)	99 (48.0)	64 (31.0)	0.743	45	55	< 0.0001	[37]
GGH 452		C/C	C/T	T/T		C	T
Japanese (Our study)	159	134 (84.3)	22 (13.8)	3 (1.9)	0.081	91	9
Japanese	142	129 (90.8)	13 (9.2)	0 (0.0)	0.568	95	5	0.1070	[20, 21]
Caucasian	571	479 (83.9)	91 (15.9)	1 (0.2)	0.119	92	8	0.0300	[27, 37, 38]
GGH−401		C/C	C/T	T/T		C	T
Japanese (Our study)	159	88 (55.3)	62 (39.0)	9 (5.7)	0.654	75	25
Japanese	257	169 (65.8)	78 (30.3)	10 (3.9)	0.790	81	19	0.1010	[21, 32]
ABCB1 3435		C/C	C/T	T/T		C	T
Japanese (Our study)	159	54 (34.0)	82 (51.6)	23 (14.4)	0.363	60	40
Japanese	174	61 (35.0)	80 (46.0)	33 (19.0)	0.460	58	42	0.4570	[9, 20]
Caucasian	769	178 (23.1)	381 (49.5)	210 (27.3)	0.838	48	52	0.0010	[27, 28, 36, 39]
ABCC2 IVS23 + 56		T/T	T/C	C/C		T	C
Japanese (Our study)	159	6 (3.8)	55 (34.6)	98 (61.6)	0.614	21	79
Caucasian	309	122 (39.5)	149 (48.2)	38 (12.3)	0.467	64	36	< 0.0001	[27, 40]
ABCG2 914		C/C	C/A	A/A		C	A
Japanese (Our study)	159	77 (48.4)	67 (42.1)	15 (9.5)	0.939	69	31
Japanese	55	30 (54.5)	20 (36.4)	5 (9.1)	0.537	73	27	0.7230	[14]
Caucasian	190	149 (78.4)	40 (21.1)	1 (0.5)	0.330	89	11	< 0.0001	[27]

Values are given as n (%). HWE: p-value for chi-square test for agreement with Hardy-Weinberg equilibrium. p-value; comparison our study (Japanese) with each ethnic/population group
MTHFR: methylenetetrahydrofolate reductase, TYMS: thymidylate synthase, RFC1: reduced folate carrier 1, FPGS: folypolyglutamayl synthase, GGH: γ-glutamyl hydrolase, ABCB1: ATP binding cassette subfamily B member 1, ABCC2: ATP binding cassette subfamily C member 2, ABCG2: ATP binding cassette subfamily G member 2

Back to article page

ISSN: 2055-0294

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com