Genetic polymorphisms in CYP1A1, CYP1B1 and COMT genes in Greenlandic Inuit and Europeans

Figures & data

Table I. Characteristics of the studied gene polymorphisms

						Activity
Gene	Chromo-some	SNP	Reference SNP	TaqMan assay	Main function	Low	High
CYP1A1	15q22–24	Ile462Val	rs1048943	C_25624888_50	Carcinogen activation; 2-hydroxylation of E2	Ile (wt)	Val (var)
CYP1B1	2p22–21	Leu432Val	rs1056836	C_3099976_30	Carcinogen activation; 4-hydroxylation of E2	Leu^a (wt)	Val^b (var)
COMT	22q11.2	Val158Met	rs4680	C_25746809_50	Estradiol catabolism	Met (var)	Val (wt)

wt: wild-type; var: variant.

^aLeu432 has the lowest 4-OH activity; but higher carcinogenic activity (21); ^b432val variant has the highest 4-OH activity; but lower carcinogenic activity (21).

Table II Characteristics of the study population

		Europeans (Men)					Greenlandic Inuit (Men and women)
		Poland	Sweden	Ukraine	All	p^a	Men	Women	All	p^b	p^c	p^d
Total	n	80	98	84	262		64	190	254
Age (years)	Median	29.3	46.6	25.1	30.9	<0.0001	29.5	55.0	52.0	<0.0001	<0.0001	<0.0001
	Min	23.5	23.8	16.2	16.2		18.3	29.0	18.3
	Max	46.3	67.5	45.3	67.5		43.2	80.0	80.0
BMI (kg/m^2)	Median	25.1	26.0	23.4	25.2	<0.0001	25.7	26.9	25.7	0.098	0.002	0.583
	Min	18.9	21.5	18.9	18.9		11.6	14.4	11.6
	Max	38.1	37.2	35.9	38.1		57.8	43.4	57.8
Smoking (current)	n (Yes/No)	42/37	57/39	67/16	166/92	0.001	53/10	116/44	169/54	0.083	0.007	0.002

^ap Value for comparison among the European countries; ^bp value for comparison between the sexes among Inuit; ^cp value for comparison between the Inuit and Europeans; ^dp value for comparison between Inuit and Europeans, men only.

Table III Genotype and allele frequencies of CYP1A1, CYP1B1 and COMT polymorphisms in Greenlandic Inuit and Europeans

		Genotypes (%)				Allele
		n	Ile/Ile	Ile/Val	Val/Val	Ile	Val	p^a
CYP1A1 (Ile462Val)	Inuit	253	73 (29)	127 (50)	53 (21)	0.540	0.460
	Europeans	229	203 (89)	26 (11)	0	0.943	0.057	0.0001
			Leu/Leu	Leu/Val	Val/Val	Leu	Val
CYP1B1 (Leu432Val)	Inuit	249	189 (76)	56 (23)	4 (1.6)	0.871	0.129
	Europeans	262	89 (34)	131 (50)	42 (16)	0.590	0.410	0.0001
			Val/Val (wtI)	Val/Met	Met/Met	Val	Met
COMT (Val158Met)	Inuit	252	44 (18)	124 (49)	84 (33)	0.421	0.579
	Europeans	261	69 (26)	133 (51)	59 (23)	0.519	0.481	0.002

^ap Value for comparison of the allele frequencies between Inuit and Europeans; no differences in allele frequencies were observed between genders (See Supplementary Table I for data).

Table IV Serum levels of CB-153 and p,p′-DDE in the study population

		Europeans (Men)					Greenlandic Inuit (Men and women)
		Poland	Sweden	Ukraine	All	p^a	Men	Women	All	p^b	p^c	p^d
CB-153 (ng/g lipid)	n	80	96	78	254		62	167	229
	Median	16	210	47	48		298	581	503
	Minimum	3	41	5	3		40	45	5
	Maximum	129	1460	198	1460	<0.0001	5455	2298	5455	<0.0001	<0.0001	<0.0001
p,p′-DDE (ng/g lipid)	Median	571	236	881	528		704	1199	1075
	Minimum	240	55	324	55		66	95	66
	Maximum	2094	2251	11791	11791	<0.0001	13197	6438	13197	<0.0001	<0.0001	0.012

^ap Value for comparison among the European countries; ^bp value for comparison between the sexes among Inuit; ^cp value for comparison between the Inuit and Europeans; ^dp value for comparison between Inuit and Europeans, men only.

Table V Comparison of CB-153 and p,p′-DDE serum concentrations in persons with different genotypes (ANCOVA)

			CYP1A1			CYP1B1			COMT
			Ile/Ile	Ile/Val	Val/Val	Leu/Leu	Leu/Val	Val/Val	Val/Val	Val/Met	Met/Met
Inuit	CB-153 (ng/g lipid)	n	60	118	51	171	53	3	39	109	80
		Median	435	532	602	567	380	403	391	508	596
		Adj mean^a	5.92	6.22	6.19	6.20	5.92	6.03	5.92	6.12	6.25
		p^b	0.008 (Ile/Ile different)			0.029 (Leu/Leu > Leu/Val)			0.034 (Val/Val < Met/Met)
	p,p′-DDE (ng/g lipid)	n	60	118	51	171	53	3	39	109	80
		Median	963	1090	1287	1153	846	1703	880	1064	1287
		Adj mean^a	6.73	7.05	6.94	7.00	6.70	7.33	6.71	6.93	7.07
		p^b	0.061			0.016 (Leu/Leu > Leu/Val)			0.040 (Val/Val < Met/Met)
Europeans	CB-153 (ng/g lipid)	n	196	26	0	87	125	42	64	131	58
		Median	60	44		33	74	86	76	45	56
		Adj mean^a	4.04	3.95		3.92	4.05	4.08	4.09	3.98	4.05
		p^b	0.571			0.421			0.647
	p,p′-DDE (ng/g lipid)	n	196	26	0	87	125	42	64	131	58
		Median	475	555		597	483	428	516	498	524
		Adj mean^a	6.15	6.20		6.32	6.19	6.06	6.33	6.18	6.14
		p^b	0.741			0.181			0.287

^aAdjusted mean based on ln-transformed data.

^bp Value for comparison of the CB-153 and p,p′-DDE between subjects with different genotypes using ANCOVA adjusting for sex, age, smoking, area of residence. Results for the pair wise comparison are given in the brackets (post hoc Bonferroni/Dunnett T3 test).

Shimada T Watanabe J Kawajiri K Sutter TR Guengerich FP Gillam EM etal Catalytic properties of polymorphic human cytochrome P450 1B1 variants Carcinogenesis 1999 20 1607 13

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