TABLE 1: DNA sequence variants of CYP3A4 found in the enhancer region, promoter region, and 3'UTR*
CYP3A4*1A |
1 |
62037 |
aaagtagtg Atggctctcat |
CYP3A4*1u‡ |
7904§ |
54133 |
ttgattatC/Aaaagaaact |
CYP3A4*1v‡ |
7601 |
54436 |
ttaaaaaaaA/-tgttactag |
CYP3A4*1B |
392 |
61645 |
agggcaA/Ggagagag |
CYP3A4*1C |
444 |
61593 |
ggcttgtT/Ggggatgaa |
CYP3A4*1D |
62 |
61975 |
gcccagC/Aaaagagca |
CYP3A4*1x |
66 |
61971 |
gcacatagcC/Gcagcaaaga |
CYP3A4*1M |
156 |
61881 |
gctgcagctC/Acagccctgc |
CYP3A4*1E |
369 |
61668 |
aatagattT/Atatgccaa |
CYP3A4*1w |
666 |
61371 |
gaaacaggcG/Atggaaacac |
CYP3A4*1K |
655 |
61382 |
tggaaacacaA/Gtggtggtaa |
CYP3A4*1L |
630 |
61407 |
aagaggacaaA/Gtaggattgc |
CYP3A4*1F |
747 |
61290 |
acagcacC/Gctggtagg |
CYP3A4*15B¶ |
844ˆ845# |
61191ˆ2 |
aagATGGAGTGAtca |
NFSE* |
246ˆ247 |
61789ˆ90 |
agtgagtgGTgtgtgtgtg |
|
219 |
61818 |
ccaacttccA/Caggtgga |
|
120 |
61917 |
aaacaatccA/Gacagcct |
|
34 |
62003 |
aaaggaagA/Tctcagagg |
3'UTR |
25958 |
87994 |
taaggacttcT/Ggctttgct |
CYP3A4*1aa |
26011 |
88049 |
aaattacttT/Ggtgaataga |
CYP3A4*1T |
26011 |
88049 |
aaattacttT/Cgtgaataga |
|
26082** |
88120 |
ttctgtacaT/Ggcattgagc |
|
26082†† |
88120 |
ttctgtacaT/Cgcattgagc |
CYP3A4*1H |
26204 |
88242 |
tccaccaccC/Accagttagc |
|
26269 |
88305 |
tcaataatttC/Tctccacaa |
|
26418 |
88454 |
ctttcctgcaC/Tattaagga |
* UTR, untranslated region; NFSE, nifedipine-specific responsive element.
† In GenBank sequence AF280107, the A in this signal is located at nucleotide number 62037.
‡ This haplotype occurs together with the G/A single nucleotide polymorphism at 82266 (refer to the footnotes to tables 2 and 3).
§ These numbers are expressed as negative in the text because these positions precede the start signal.
¶ A variant of CYP3A4*15A.
# The chevron indicates a nucleotide insertion.
** Data from Dai et al. (35).
†† Data from Lamba et al. (30).
TABLE 2:
DNA sequence variants of CYP3A4 found in the coding region
CYP3A4*14 |
44 |
62080 |
gcttctccT/Cggctgt |
L15P |
1 |
CYP3A4*7 |
6004 |
68040 |
tcccaggG/Acttttgt |
G56D |
3 |
CYP3A4*4 |
13871 |
75907 |
aagtgccA/Gtctctat |
I118V |
5 |
CYP3A4*8 |
13908 |
75944 |
agattacG/Aatcattg |
R130Q |
5 |
CYP3A4*15A |
14269 |
76305 |
tctgaggcG/Aggaag |
R162Q |
6 |
CYP3A4*9 |
14292 |
76328 |
gcaagcctG/Atcacct |
V170I |
6 |
CYP3A4*10 |
14304 |
76340 |
ccttgaaaG/Cagtaag |
D174H |
6/7 |
CYP3A4*16‡ |
15603 |
77639 |
tgtgatcaC/Gtagcac |
T185S |
7 |
CYP3A4*17 |
15615 |
77651 |
cacatcatT/Ctggagt |
F189S |
7 |
CYP3A4*5 |
15702 |
77738 |
ttttggatcC/Gattcttt |
P218R |
7 |
CYP3A4*2 |
15713 |
77749 |
attctttctcT/Ccaataa |
S222P |
7 |
CYP3A4*6 |
17662ˆ3 § |
79698ˆ9 |
gatgattgacˆAtctcag |
277ˆS278I (285 Stop)¶ |
9 |
CYP3A4*18‡ |
20070 |
82106 |
ctgtccgatcT/Cggag |
L293P |
10 |
CYP3A4*11‡ |
21867 |
83903 |
gaatgaaaC/Tgctcaga |
T363M |
11 |
CYP3A4*12 |
21896 |
83932 |
gctatgagaC/Tttgaga |
L373F |
11 |
CYP3A4*13 |
22026 |
84062 |
agttcctccC/Ttgaaagg |
P416L |
11 |
CYP3A4*3 |
23172 |
85208 |
gcattggcaT/Cgaggttt |
M445T |
12 |
CYP3A4*19# |
23237 |
85273 |
tccttcaaaC/Tcttgtaa |
P467S |
12 |
Trivial** |
|
|
|
|
|
CYP3A4 682C/T |
15628 |
77664 |
gagtgaacatC/Tgactct |
I193I†† |
7 |
|
20083 |
82119 |
ctcgtggcC/Tcaatcgaa |
A297A |
10 |
|
21817 |
83853 |
ccacccacC/Atatgata |
T346T |
11 |
M15 |
21868 |
83904 |
tgaatgaaacG/Actcaga |
T363T |
11 |
M18 |
25925 |
87961 |
gggatggcacC/Tgtaagt |
T499T |
13 |
* Refer to the Human Cytochrome P450 (CYP) Allele Nomenclature Committee website
(http//www.imm.ki.se/cypalleles).
† Relative to A at nucleotide 62037 in GenBank sequence AF280107.
‡ Haplotypes CYP3A4*11b, *11c, *16B, and *18B have been described recently (24).
§ The chevron indicates a nucleotide insertion.
¶ The A insertion causes a frame shift, and a stop codon results 7–8 codons downstream.
# Refer also to table 3, footnote.§
** Names given in original publications.
†† Silent changes.
TABLE 3: DNA sequence variants of CYP3A4 found in introns
CYP3A4*1y |
3856 |
65993 |
tatctataaA/-gtcacaatc |
1 |
T5922C‡ |
5917 |
67953 |
tctgatttcaT/Ctggcttcg |
2 |
CYP3A4*1J |
6076 |
68113 |
gaaacttccA/Gttggataga |
3 |
T6165A |
6159 |
68195 |
gggatgaagctcT/Atgtca |
3 |
SNP4 |
13804 |
75840 |
ccacaactgA/Ttgtaggaca |
4 |
G13875A |
13757 |
75793 |
tgaataagtG/Attcctgttta |
4 |
G13947C |
13829 |
75865 |
tgtttctgctttG/Caactctag |
4 |
SNP5 |
14200 |
76236 |
tatgggtggtgT/Gtgtgtttt |
5 |
M10 |
14323 |
76359 |
aagcgcagcC/Tatggggtt |
6 |
M11 |
14329 |
76365 |
gccatgggG/ttctgagctgtc |
6 |
T14475G |
14357 |
76393 |
cccctccagcT/Ggcctgcca |
6 |
CYP3A4*1z |
15552 |
77589 |
taattttccA/Ccatctttct |
6 |
CYP3A4*1P |
15726 |
77763 |
aagtatgtgG/Aactactatt |
7 |
T15871G |
15753 |
77789 |
ttttatttatcttT/Gctctcttaaa |
7 |
T15901C |
15783 |
77819 |
tttattgagaT/Cataaatcacca |
7 |
SNP10 |
15804 |
77840 |
tgtaattcaT/Gccacttaaaa |
7 |
CYP3A4*1Q |
15808 |
77845 |
ttcatccacT/Ctaaaatata |
7 |
T15955A |
15837 |
77873 |
gtgatttgtagT/Aacatttgaag |
7 |
CYP3A4*1R |
16774 |
78811 |
acattcacaA/Gtgaatttct |
7 |
C17141T |
17024 |
79060 |
gtgcagttacC/Ttgtatgttttta |
8 |
CYP3A4*11b |
17717 |
79754 |
tttctgaggG/Actacttgtg |
9 |
SNP14 |
17815/6 |
79851/2 |
agaacgacacAT/-gtttgaat |
9 |
G20338A§ |
20230 |
82266 |
tgagtggatgG/Atacatggag |
10 |
SNP16 |
20265 |
82301 |
GaaaccttagC/Taaaaatgcc |
10 |
G20417C |
20309 |
82345 |
tttttataaaaaG/Ccataatcact |
10 |
A21891C |
21785 |
83821 |
caatttatccaA/Catctgtttcgt |
10 |
SNP18 |
21795 |
83831 |
caaatctgtttcG/Attctttccagg |
10 |
M16 |
22041 |
84077 |
aggtacaaggC/Tccctgggaa |
11 |
SNP21 |
23024 |
85060 |
aagtaagaaA/Gccctaacatg |
11 |
C23187T |
23081 |
85117 |
aaaaatctaccaaC/Tgtggaac |
11 |
* Trivial names given in original publications, unless italicized.
† Relative to A at nucleotide 62037 in GenBank sequence AF280107.
‡ The four- and five-digit designations are reportedly from GenBank sequence AF209389 (Lamba et al. (30)).
§ This polymorphism occurs with P467S (table 2), and the haplotype is designated CYP3A4*19. When this polymorphism occurs absent P457S, it is designated CYP3A4*1G (24).
TABLE 4: Reported frequencies of CYP3A4*1B
|
AA |
AG |
GG |
|
|
|
|
Caucasians (94) |
79 |
12 |
3 |
0.096 (0.054, 0.138) |
6.49 |
0.011 |
Rebbeck et al., 1998 (26) |
Prostate cancer (230) |
188 |
42‡ |
|
|
|
|
|
African Americans (70) |
15 |
36 |
9 |
0.530 (0.447, 0.613) |
0.714 |
0.789 |
Walker et al., 1998 (36) |
Caucasians (132) |
114 |
13 |
5 |
0.087 (0.053, 0.121) |
19.15 |
10 –5 |
|
Chinese (130) |
130 |
0 |
0 |
0.000 |
|
|
|
Caucasians§ (39) |
36 |
3 |
0 |
0.038 (0, 0.081) |
0.062 |
0.803 |
Westlind et al., 1999 (27) |
Japanese (128) |
128 |
0 |
0 |
0.000 |
|
|
Ando et al., 1999 (37) |
Caucasians (273) |
526/20¶ |
|
|
0.036 (0.020, 0.052) |
|
|
Ball et al., 1999 (38) |
Hispanics (188) |
341/35¶ |
|
|
0.093 (0.064, 0.122) |
|
|
|
African Americans (186) |
169/203¶ |
|
|
0.546 (0.495, 0.597) |
|
|
|
African Americans (90) |
59/121¶ |
|
|
0.672 (0.603, 0.741) |
|
|
|
Chinese (78) |
78 |
0 |
0 |
0.000 |
|
|
|
Japanese (77) |
77 |
0 |
0 |
0.000 |
|
|
|
Asians (80) |
80 |
0 |
0 |
0.000 |
|
|
Paris et al., 1999 (39) |
Caucasians (117) |
109 |
7 |
1 |
0.038 (0.013, 0.063) |
4.273 |
0.039 |
|
Hispanics (121) |
97 |
22 |
2 |
0.107 (0.068, 0.146) |
0.327 |
0.567 |
|
African Americans (116) |
22 |
62 |
32 |
0.543 (0.479, 0.607) |
0.687 |
0.407 |
|
African Americans/prostate cancer (174) |
30 |
64 |
80 |
0.644 (0.594, 0.694) |
6.832 |
0.009 |
|
Caucasians (101) |
90 |
11 |
0 |
0.054 (0.023, 0.085) |
0.335 |
0.563 |
Tayeb et al., 2000 (43) |
Saudis (101) |
84 |
16 |
1 |
0.089 (0.050, 0.128) |
0.059 |
0.808 |
|
Ghanians (100) |
13 |
36 |
51 |
0.690 (0.626, 0.754) |
2.512 |
0.113 |
|
African Americans (75) |
6 |
38 |
31 |
0.667 (0.592, 0.742) |
1.470 |
0.225 |
Sata et al., 2000 (28) |
Caucasians (59) |
54 |
5 |
0 |
0.042 (0.006, 0.078) |
0.120 |
0.734 |
|
Chinese (59) |
59 |
0 |
0 |
0.000 |
|
|
|
African Americans (15) |
1 |
4 |
10 |
0.800 (0.657, 0.943) |
0.416 |
0.519 |
Wandel et al., 2000 (44) |
Caucasians (56) |
45 |
11 |
0 |
0.196 (0.141, 0.251) |
0.664 |
0.451 |
Tayeb et al., 2002 (82) |
Caucasians/prostate cancer (28) |
11 |
17 |
0 |
0.304 (0.184, 0.424) |
4.797 |
0.021 |
|
Caucasians (101) |
90 |
9 |
2 |
0.064 (0.030, 0.098) |
6.830 |
0.009 |
Garcia-Martin 2002 (40) |
Caucasians (53) |
99/7¶ |
|
|
0.065 (0.018, 0.112) |
|
|
Lamba et al., 2002 (30) |
African Americans (21) |
22/20¶ |
|
|
0.480 (0.329, 0.631) |
|
|
|
Caucasians (340) |
300 |
26 |
14 |
0.079 (0.061, 0.102) |
77.355 |
<10 –6 |
Zeigler-Johnson et al., 2002 (45) |
African Americans (130) |
27 |
52 |
51 |
0.592 (0.532, 0.650) |
3.836 |
0.050 |
|
Ghanians# (118) |
7 |
32 |
79 |
0.810 (0.750, 0.851) |
2.180 |
0.140 |
|
Senegalese# (173) |
14 |
47 |
112 |
0.780 (0.737, 0.823) |
6.913 |
0.009 |
|
Caucasians ( Australia) |
|
|
|
|
|
|
Spurdle et al., 2002 (80) |
Controls (breast cancer) |
468 |
31 |
1 |
0.033 (0.022, 0.044) |
0.408 |
0.523 |
|
Breast cancer |
899 |
52 |
0 |
0.027 (0.020, 0.035) |
0.751 |
0.386 |
|
Controls (ovarian cancer) |
260 |
15 |
1 |
0.031 (0.016, 0.045) |
2.217 |
0.136 |
|
Ovarian cancer |
449 |
38 |
1 |
0.041 (0.029, 0.053) |
0.043 |
0.835 |
|
Caucasians |
|
|
|
|
|
|
Tayeb et al., 2003 (83) |
Benign prostatic hyperplasia (379) |
344 |
35 |
0 |
0.046 (0.031, 0.061) |
0.888 |
0.346 |
|
Benign prostatic hyperplasia/prostate cancer (21) |
16 |
4 |
1 |
0.143 (0.034, 0.251) |
1.037 |
0.309 |
|
Caucasians** |
|
|
|
|
|
|
Plummer et al., 2003 (25) |
Prostate cancer (390) |
362 |
24 |
4 |
0.041 (0.027, 0.055) |
0.082 |
0.774 |
|
Controls (426) |
391 |
34 |
1 |
0.042 (0.028, 0.056) |
18.519 |
<10 –4 |
|
African Americans** |
|
|
|
|
|
|
Plummer et al., 2003 (25) |
Prostate cancer (38) |
11 |
13 |
14 |
0.539 (0.427, 0.652) |
0.707 |
0.401 |
|
Controls (38) |
8 |
16 |
14 |
0.579 (0.468, 0.690) |
3.687 |
0.055 |
|
Japanese |
|
|
|
|
|
|
Fukushima et al., 2004 (24) |
Hospital patients (416) |
416 |
0 |
0 |
0.000 |
|
|
|
* F, variant allele frequency.
† CI, confidence interval.
‡ Heterozygote and variant homozygotes were collapsed to compare prostate cancer cases with controls.
§ No specific details of race/ethnicity were given; samples were collected at surgery or autopsy at a hospital in Gothenburg, Sweden.
¶ Numbers in these lines are alleles (A/G); it was impossible to deduce full genotypes. Consequently, Hardy-Weinberg equilibrium was also unavailable.
# In the original publication (45), Africans from modern-day Africa were further divided into tribal groups.
** Sibling-pair case-control design (the Caucasian control group may contain related persons).
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