Table 1 Common star alleles in selected cytochrome P450 genes across Shetland and Orkney cohorts in comparison with other European populations. Rare alleles in these genes are presented in Supplementary table 2.

From: Characterisation of pharmacogenomic variation in the Shetland and Orkney Isles in Scotland

Star alleles

Defining variants

CPIC/known

clinical function

Frequencies (%)

Shetland

Orkney

European

(1000G)

European

(ClinPGx)b

CYP2A6

*1

Reference haplotype

Normal enzyme activity

48.8

44.1

51.3

n/a

*2

rs1801272 (L160H)

Substantially decreased

enzyme activity

3.7

3.0

3.2

n/a

*9

rs28399433 (TATA Box)

Decreased mRNA expression

6

8.1

7.0

n/a

*14

rs28399435 (S29N)

Unknown

2.8

2.3

3.2

n/a

*18

rs1809810 (Y392F)

Decreased enzyme activity

1.1

2.2

1.4

n/a

*21

rs6413474 (K476R)

Decreased enzyme activity

0.8

1.9

1.2

n/a

*35

rs143731390 (N438Y),

3’-UTR conversion (expression)

Decreased enzyme activity

5.8

2.6

0.8

n/a

*46

3’-UTR conversion (expression)

Increased mRNA stability

27.7

34.2

27.2

n/a

CYP2B6

*1

Reference haplotype

Normal

51.1

54.8

53.4

49.1

*2

rs8192709 (R22C)

Normal

6.4

5.3

5.2

4.9

*4

rs2279343 (K262R)

Increased

1.7

1.0

3.1

4.1

*5

rs3211371 (R487C)

Normal

12.5

10.7

10.8

11.5

*6

rs3745274 (Q172H, splice defect), rs2279343 (K262R)

Decreased

17.3

16

22.1

23.3

*7

rs3745274 (Q172H, splice defect), rs2279343 (K262R), rs3211371 (R487C)

Decreased

3.1

2.9

0

2.5

*9

rs3745274 (Q172H, splice defect)

Decreased

2.0

3.8

0.6

1.5

*11

rs35303484 (M46V)

Uncertain

1.1

1.0

0.4

0.3

*15

rs35979566 (I391N)

Uncertain

0.9

1.6

0.4

0.7

*22

rs34223104 (expression)

Increased

1.9

0.9

0.9

1.4

CYP2C19

*1

rs3758581 (I331V)

Normal

59.6

59.8

54.8

62.5

*2

rs12769205 (splicing defect), rs4244285 (splicing defect), rs3758581 (I331V)

No function

13.3

11.0

14.8

14.7

*17

rs12248560 (expression), rs3758581 (I331V)

Increased

20.3

20.5

22.5

21.5

*38

Reference haplotype

Normal

5.6

7.0

6.8

 

CYP2C9

*1

Reference haplotype

Normal

81.4

84.3

78.7

79.3

*2

rs1799853 (R144C)

Decreased

12

7.9

12.9

12.7

*3

rs1057910 (I359L)

No function

5.6

7.4

7.3

7.6

CYP2C8

*1

Reference haplotype

Normal

79.4

87.8

81.6

n/a

*3

rs11572080 (R139K), rs10509681 (K399R)

Uncertain

12.5

7.7

12.3

n/a

*4

rs1058930 (I264M)

Uncertain

5.8

4.1

5.6

n/a

*15

rs41286886 (V181I)

Uncertain

2.1

0

0

n/a

CYP2D6

*1

Reference haplotype

Normal

33

36.8

35.9

28.5

*2

rs16947 (R296C), rs1135840 (S486T)

Normal

14.2

13.7

15.7

18.5

*2x2

Duplication of *2

Increased

0.4

0.3

1.7

1.2

*3

rs35742686 (frameshift)

No function

1.5

1.6

1.3

1.6

*4

rs3892097 (splicing defect)

No function

17.6

15.9

11.3

18.5

*4xN

Duplication of *4

No function

2

2.1

1.1

0.7

*68+*4

CYP2D6-2D7 hybrid (intron 1 switch point) in tandem with *4

No function

2.8

2.5

5.9

 

*5

Full gene deletion

No function

3.5

4.4

2.4

2.9

*6

rs5030655 (frameshift)

No function

0.9

1.3

2.2

1.1

*9

rs5030656 (K281del)

Decreased

4.8

4.7

2.4

2.8

*10

rs1065852 (P34S), rs1135840 (S486T)

Decreased

0.3

0.8

1.3

1.6

*28

rs72549358 (V7M), rs78482768 (Q151E), rs16947 (R296C), rs1135840 (S486T)

Uncertain

0.8

1

0.5

0.4

*33

rs28371717 (A237S)

Normal

1.3

0.4

0.6

1.0

*35

rs769258 (V11M), rs16947 (R296C), rs1135840 (S486T)

Normal

8

4.5

5

5.5

*41

rs16947 (R296C), rs28371725 (splicing defect), rs1135840 (S486T)

Decreased

4.9

4.8

8.4

9.2

*59

rs16947 (R296C), rs79292917 (splicing defect), rs1135840 (S486T)

Decreased

1

0.8

0.2

0.4

CYP2E1b

*4

rs6413419-A (V179I)

Uncertain

1.4

2.2

3.2

n/a

*1x2

Gene duplication

Uncertain

1.1

1.4

1.0

n/a

CYP3A4

*1

Reference haplotype

Normal

93.6

92

93.7

n/a

*3

rs11572080 (R139K), rs10509681 (K399R)

Uncertain

0.5

1.2

0.7

n/a

*10

rs1058930 (I264M)

Uncertain

0.6

1.3

0.3

n/a

*22

rs41286886 (V181I)

Uncertain

4.9

5.4

4.5

n/a

CYP3A5

*1

Reference haplotype

Normal

3.5

9.9

4.9

7.4

*3

rs776746 (splice defect)

No function

96.5

90.1

94.8

92.4

CYP4F2

*1

Reference haplotype

Normal

61

58.1

57.5

56.6

*3

rs2108622 (V433M)

Unknown

11.1

15.4

11.3

27.5

*4

rs2108622 (V433M), rs3093105 (W12G)

Unknown

14.3

12.4

17.6

 

*5

rs3093200 (L519M)

Unknown

6.3

6.7

5.9

 

*6

rs3093153 (G185V)

Unknown

4.6

5

6.7

 

*14

rs145174239 (L341V)

Unknown

1.6

1.5

0.3

 
  1. aCYP2E1 star allele nomenclature has not been fully curated/updated since 2013.
  2. bNumber of participants in ClinPGx aggregate analyses vary (CYP2B6: n=69572, CYP2C19: n=71782, CYP2C9: n≈91200, CYP2D6: n=65090, CYP3A5: n=5607, CYP4F2: n=77524).
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