Table 2 Star alleles in selected non-cytochrome P450 pharmacogenes across Shetland and Orkney cohorts in comparison with other European populations.

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

Star alleles

Defining variants

CPIC/Known clinical functiona

Frequencies (%)

Shetland

Orkney

1000G European datasets

European

(ClinPGx)b

GSTM1

*A

Reference haplotype

Normal

18.5

13.0

18.2

n/a

*B

rs1065411 (K173N)

Normal

7.9

7.7

8.1

n/a

*0

GSTM1 deletion

No function

72.7

77.6

71.6

n/a

*Ax2

Duplication of *A

Increased activity

0

0

0.2

n/a

*Bx2

Duplication of *B

Increased activity

0.2

<0.1

0

n/a

GSTT1

*A

Reference haplotype

Normal

42.4

42.5

59.3

n/a

*0

GSTT1 deletion

No function

57.4

57.5

39.9

n/a

*Ax2

GSTT1 duplication

Increased activity

0

0

0.2

n/a

NAT1

*3

rs15561-A

Uncertain

3.2

3.9

2.0

n/a

*4

rs15561-C, rs1057126-T

Normal

75.0

73.8

69.4

n/a

*10

rs15561-A, rs1057126-A

Increased activity

16.0

18.8

21.8

n/a

*11 (including *11A, 11B and *11C)

rs4987076 (V149I), rs4986783 (S214A), rs4986990 (T153T), rs72554666 (delAATAATAAA), rs15561-A

Increased activity

1.8

1.5

2.3

n/a

*14A and *14B

rs4986782 (R187Q), rs15561-A, rs1057126-A

Decreased activity

2.4

1.0

2.1

n/a

*15

rs5030839 (R187*)

No function

0.4

0.2

0.9

n/a

*17

rs56379106 (R64W)

Decreased activity

0.4

0.5

0.5

n/a

*18A

rs4646271-delAAA, rs1057126-A, rs15561-A

Uncertain

0

0.1

0.4

n/a

*22

rs56172717 (D251V)

Decreased activity

0

0

0.5

n/a

*29

rs15561-A, rs1057126-A, rs8190859

Uncertain

0.8

0.1

0

n/a

NAT2

*1

Reference haplotype

Rapid acetylation

0.3

1.2

0.4

n/a

*4

rs1208 (R268K)

Rapid acetylation

6.5

19.5

24.2

n/a

*5

rs1801280 (I114T)

Slow acetylation

40.9

39.2

43.2

n/a

*6

rs1799930 (R197Q), rs1208 (R268K)

Slow acetylation

41.4

33.9

30.0

n/a

*7

rs1208 (R268K), rs1799931 (G286E)

Slow acetylation

3.1

2.1

2.4

n/a

*14

rs1801279 (R64Q), rs1208 (R268K)

Slow acetylation

0

0

0.1

n/a

*16

rs1801280 (I114T), rs1208 (R268K)

Slow acetylation

5.7

3.5

1.7

n/a

*30

rs1801280 (I114T), rs1799930 (rs1799930), rs1208 (R268K)

Slow acetylation

0

<0.1

0

n/a

*34

rs1799930 (R197Q)

Slow acetylation

0

0.4

0

n/a

*40

rs1799931 (G286E)

Unknown

0

<0.1

0

n/a

NUDT15

*1

Reference haplotype

Normal

98.2

99.3

99.8

99.3

*3

rs116855232 (R139C)

No function

0.4

0.1

0.2

0.2

*4

rs147390019 (R139H)

Unknown

0

<0.1

0

<0.1

*12

rs149436418 (F52L)

Unknown

1.4

0.5

0

 

SLCO1B1

*1

Reference haplotype

Normal

57.8

59.6

56.6

40.3

*4

rs11045819 (P155T)

Unknown

0

0.2

0.1

 

*5

rs4149056 (V174A)

No function

2.9

2.7

2.7

2.0

*14

rs2306283 (N130D), rs11045819 (P155T)

Increased

12.9

15.8

14.1

13.6

*15

rs2306283 (N130D), rs4149056 (V174A)

No function

11.4

11.4

13.0

15.0

*19

rs34671512 (L643F)

Unknown

0.4

0.8

0.3

 

*20

rs2306283 (N130D), rs34671512 (L643F)

Increased

7.5

5.6

4.8

3.7

*37

rs2306283 (N130D)

Normal

7.0

3.9

8.0

25.3

*40

rs4149056 (V174A), rs34671512 (L643F)

Uncertain

0

<0.1

0

 

*46

rs2306283 (N130D), rs4149056 (V174A), rs71581941 (R580X)

No function

0

0

0.2

 

*48

SLCO1B1 gene deletion

No function

0

<0.1

0

 

TPMT

*1

Reference haplotype

Normal

95.6

(*1S=21.9)

95.4

(*1S=21.2)

95.9

(*1S=20.9)

95.3

*2

rs1800462 (Ala80Pro)

No function

0.2

0.1

0.6

0.2

*3A

rs1800460 (Ala154Thr), rs1142345 (Tyr240Cys)

No function

3.8

3.2

1.6

3.4

*3B

rs1800460 (Ala154Thr)

No function

0

0.04

0

0.3

*3C

rs1142345 (Tyr240Cys)

No function

0.3

0.1

0.1

0.5

*3E

rs1800460 (Ala154Thr), rs2842934 (Ile158Ile), rs1142345 (Tyr240Cys)

No function

0

0.9

1.1

 

*9

rs151149760 (Lys119Thr)

Uncertain

0.1

0.1

0

<0.1

*12

rs200220210 (S125L)

Uncertain

0

0

0.1

 

*16

rs144041067 (R163P)

Uncertain

0

0

0.2

0.1

*21

rs200591577 (L69V)

Uncertain

0

0

0.1

<0.1

*32

rs115106679 (E114K)

Uncertain

0

0

0.1

<0.1

*33

rs112339338 (R163C)

Uncertain

0

0

0.1

<0.1

UGT1A1

   

Shetland

Orkney

1000G European datasets

European

(ClinPGx),

n=1550

*1

Reference haplotype

Normal

50.5

58.6

56.4

36.1

*6

rs4148323 (G71R)

Decreased function

0

0

0.6

0.8

*28

rs3064744 (A[TA]6TAA>A[TA]7TAA; expression)

Decreased function

0

0.4

0.3

31.6b

*28+*80

rs887829 + rs3064744 (A[TA]6TAA>A[TA]7TAA; expression)

Decreased function

32.8

23.6

27.6

*80

rs887829

Unknown

0.3

1.1

0

*36

rs3064744-delTA

Increased function

0

0.3

0.3

0.0

*37+*80

rs887829 + rs3064744 (A[TA]6TAA>A[TA]8TAA; expression)

Unknown

0.3

0

0

 

*65

rs28899472

Unknown

0.5

0.2

0.5

 

*66

rs2302538

Unknown

11.3

12.6

11.8

 
  1. aFunctional impacts of alleles in GST genes, NAT genes, TPMT, UGT1A1 were obtained from published literature.
  2. +Number of participants in ClinPGx aggregate analyses vary (NUDT15: n≈52267, SLCO1B1: n≈60448, TPMT: n≈95315, UGT1A1: n=1550).
  3. cThe UGT1A1*28 frequency in the ClinPGx reference materials is reported as ~31.6% and that for UGT1A1*80 is reported as ~31.4%, but the *28 allele is known to be in high linkage disequilibrium with *80.
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