Human NAT2 Alleles (Haplotypes)

 

 

Last updated 18/04/2016

 

 

NAT2 Allele (Haplotype)a,b

Nucleotide Change(s)

and rs Identifiersc

Amino Acid Change(s)

Phenotyped

References

NAT2*4

Reference

Reference

Rapid

1-17

 

NAT2*5A

341T>C (rs1801280)
481C>T (rs1799929)

I114T

L161L (synonymous)

Slow

2,9,10,18,19

NAT2*5B

341T>C (rs1801280)
481C>T (rs1799929)
803A>G (rs1208)

I114T
L161L (synonymous)

K268R

Slow

3, 9-17,19,20

NAT2*5C

341T>C (rs1801280)
803A>G (rs1208)

I114T
K268R

Slow

9,10,18,19,21,22

NAT2*5D

341T>C (rs1801280)

I114T

Slow

12,15,17,23-26

NAT2*5E

341T>C (rs1801280)
590G>A (rs1799930)

I114T
R197Q

Slow

23

NAT2*5F

341T>C (rs1801280)
481C>T (rs1799929)
759C>T (rs56011192)
803A>G (rs1208)

I114T
L161L (synonymous)

V253V (synonymous)

K268R

Slow

27

NAT2*5G

282C>T (rs1041983)
341T>C (rs1801280)
481C>T (rs1799929)
803A>G (rs1208)

Y94Y (synonymous)

I114T
L161L (synonymous)

K268R

Slow

28

NAT2*5H

341T>C (rs1801280) 
481C>T (rs1799929)
803A>G (rs1208)
Δ859

I114T
L161L (synonymous)

K268R
S287 Frameshift

Slow

28

NAT2*5I

341T>C (rs1801280)
411A>T (rs4986997)
481C>T (rs1799929) 
803A>G (rs1208)

I114T
L137F
L161L (synonymous)

K268R

Slow

16

NAT2*5Je

282C>T (rs1041983)
341T>C (rs1801280)

590G>A (rs1799930)

Y94Y (synonymous)

I114T
R197Q

Slow

29

NAT2*5K

282C>T (rs1041983)
341T>C (rs1801280) 

Y94Y (synonymous)

I114T

 

30

NAT2*5KAf

282C>T (rs1041983)

341T>C (rs1801280)

857G>A (rs1799931)

 

Y94Y (synonymous)

I114T

G286E

 

60

NAT2*5L

70T>A (rs45477599)

341T>C (rs1801280) 

481C>T (rs1799929)

803A>G (rs1208)

L24I

I114T
L161L (synonymous)

K268R

 

30,31

NAT2*5M

341T>C (rs1801280) 

481C>T (rs1799929)

803A>G (rs1208)

838G>A (rs56393504)

I114T
L161L (synonymous)

K268R

V280M

 

32

NAT2*5N

341T>C (rs1801280) 

472A>C (rs139351995)

481C>T (rs1799929)

803A>G (rs1208)

I114T

I158L

L161L (synonymous)

K268R

 

33

NAT2*5O

203G>A (rs72466458)

341T>C (rs1801280) 

481C>T (rs1799929)

803A>G (rs1208)

C68Y

I114T
L161L (synonymous)

K268R

 

33

NAT2*5P

282C>T (rs1041983)
341T>C (rs1801280)
481C>T (rs1799929)
578C>T (rs79050330)

590G>A (rs1799930)

803A>G (rs1208)

Y94Y (synonymous)

I114T
L161L (synonymous)

T193M

R197Q

K268R

 

34

NAT2*5Qf

341T>C (rs1801280)

590G>A (rs1799930)

803A>G (rs1208)

I114T

R197Q

K268R

 

35

NAT2*5Rf

282C>T (rs1041983)

341T>C (rs1801280)

590G>A (rs1799930)

803A>G (rs1208)

Y94Y (synonymous)

I114T

R197Q

K268R

 

35

NAT2*5Sf

341T>C (rs1801280)

857G>A (rs1799931)

I114T

G286E

 

35

NAT2*5Tf

282C>T (rs1041983)

341T>C (rs1801280)

803A>G (rs1208)

Y94Y (synonymous)

I114T

K268R

 

35

NAT2*5TAf

282C>T (rs1041983)

341T>C (rs1801280)

803A>G (rs1208)

857G>A (rs1799931)

 

Y94Y (synonymous)

I114T

K268R

G286E

 

60

NAT2*5Uf

282C>T (rs1041983)

341T>C (rs1801280)

481C>T (rs1799929)

590G>A (rs1799930)

803A>G (rs1208)

Y94Y (synonymous)

I114T

L161L (synonymous)

R197Q

K268R

 

35

NAT2*5Vf

282C>T (rs1041983)

341T>C (rs1801280)

481C>T (rs1799929)

Y94Y (synonymous)

I114T

L161L (synonymous)

 

35

NAT2*5VAf

282C>T (rs1041983)

341T>C (rs1801280)

481C>T (rs1799929)

857G>A (rs1799931)

 

Y94Y (synonymous)

I114T

L161L (synonymous)

G286E

 

60

NAT2*5Wf

341T>C (rs1801280)

354T>C (rs146405047)

481C>T (rs1799929)

803A>G (rs1208)

 

I114T

N118N (synonymous)

L161L (synonymous)

K268R

 

60

NAT2*5Xf

341T>C (rs1801280)

403C>G (rs12720065)

481C>T (rs1799929)

803A>G (rs1208)

 

I114T

L135V

L161L (synonymous)

K268R

 

60

NAT2*5Yf

341T>C (rs1801280)

481C>T (rs1799929)

622T>C (rs56387565)

803A>G (rs1208)

 

I114T

L161L (synonymous)

Y208H

K268R

 

60

NAT2*5Zf

191G>A (rs1801279)

341T>C (rs1801280)

481C>T (rs1799929)

R64Q

I114T

L161L (synonymous)

 

60

 

 

 

NAT2*6A

282C>T (rs1041983)
590G>A (rs1799930)

Y94Y (synonymous)

R197Q

Slow

1-3,9-17,19,22

NAT2*6B

590G>A (rs1799930)

R197Q

Slow

12,15,17,19,24,25

NAT2*6C

282C>T (rs1041983)
590G>A (rs1799930)
803A>G (rs1208)

Y94Y (synonymous)

R197Q
K268R

Slow

24,25,30,36

NAT2*6D

111T>C (rs72554615)
282C>T (rs1041983)
590G>A (rs1799930)

F37F (synonymous)

Y94Y (synonymous)

R197Q

Slow

26

NAT2*6E

481C>T (rs1799929)
590G>A (rs1799930)

L161L (synonymous)

R197Q

Slow

37

NAT2*6F

590G>A (rs1799930)

803A>G (rs1208)

R197Q
K268R

 

31

NAT2*6G

282C>T (rs1041983)

518A>G

590G>A (rs1799930)

Y94Y (synonymous)

K173R

R197Q

 

31

NAT2*6H

282C>T (rs1041983)

590G>A (rs1799930)

766A>G (rs55700793)

Y94Y (synonymous)

R197Q

K256E

 

31,33

NAT2*6I

282C>T (rs1041983)

590G>A (rs1799930)

838G>A (rs56393504)

857G>A (rs1799931)

Y94Y (synonymous)

R197Q

V280M

G286E

 

31

NAT2*6J

282C>T (rs1041983)

590G>A (rs1799930)

857G>A (rs1799931)

Y94Y (synonymous)

R197Q

G286E

 

32

NAT2*6K

282C>T (rs1041983)

590G>A (rs1799930)

638C>T (rs138707146)

Y94Y (synonymous)

R197Q

P213L

 

32

NAT2*6L

282C>T (rs1041983)

345C>T (rs45532639)

590G>A (rs1799930)

Y94Y (synonymous)

D115D(synonymous)

R197Q

 

32

NAT2*6M

152G>T (rs72466457)

282C>T (rs1041983)

590G>A (rs1799930)

G51V

Y94Y (synonymous)

R197Q

 

33

NAT2*6N

282C>T (rs1041983)

481C>T (rs1799929)

590G>A (rs1799930)

Y94Y (synonymous)

L161L (synonymous)

R197Q

 

38

NAT2*6Of

282C>T (rs1041983)

590G>A (rs1799930)

838G>A (rs56393504)

Y94Y (synonymous)

R197Q

V280M

 

39

NAT2*6Pf

403C>G (rs12720065)

590G>A (rs1799930)

L135V

R197Q

 

40

NAT2*6Qf

282C>T (rs1041983)

308C>T

590G>A (rs1799930)

Y94Y (synonymous)

T103I

R197Q

 

40

NAT2*6Rf

282C>T (rs1041983)

481C>T (rs1799929)

590G>A (rs1799930)

803A>G (rs1208)

Y94Y (synonymous)

L161L (synonymous)

R197Q

K268R

 

35

NAT2*6Sf

590G>A (rs1799930)

857G>A (rs1799931)

R197Q

G286E

 

35

NAT2*6Tf

481C>T (rs1799929)

590G>A (rs1799930)

857G>A (rs1799931)

L161L (synonymous)

R197Q

G286E

 

 

35

NAT2*6Uf

282C>T (rs1041983)

590G>A (rs1799930)

579G>T (rs144176822)

 

Y94Y (synonymous)

R197Q

T193T (synonymous)

 

60

NAT2*6Vf

403C>G (rs12720065)

590G>A (rs1799930)

838G>A (rs56393504)

 

L135V

R197Q

V280M

 

60

 

NAT2*7A

857G>A (rs1799931)

G286E

Slow; Substrate dependent?

2,11,12,15,17,19,36

NAT2*7B

282C>T (rs1041983)
857G>A (rs1799931)

Y94Y (synonymous)

G286E

Slow; Substrate dependent?

1,9-18,36

NAT2*7C

282C>T (rs1041983)
803A>G (rs1208)

857G>A (rs1799931)

Y94Y (synonymous)

K268R

G286E

 

34,40

NAT2*7D

191G>A (rs1801279)
282C>T (rs1041983)
857G>A (rs1799931)

R64Q

Y94Y (synonymous)

G286E

 

33

NAT2*7Ef

282C>T (rs1041983)

481C>T (rs1799929)

857G>A (rs1799931)

Y94Y (synonymous)

L161L (synonymous)

G286E

 

39

NAT2*7Ff

282C>T (rs1041983)

481C>T (rs1799929)

803A>G (rs1208)

857G>A (rs1799931)

Y94Y (synonymous)

L161L (synonymous)

K268R

G286E

 

35

NAT2*7Gf

226T>G

282C>T (rs1041983)

857G>A (rs1799931)

Y76D

Y94Y (synonymous)

G286E

 

59

 

NAT2*10

499G>A (rs72554617)

E167K

Slow; Substrate dependent?

11,15-17

 

NAT2*11A

481C>T (rs1799929)

L161L (synonymous)

Rapid

12,15,17,41

NAT2*11B

481C>T (rs1799929)
Δ859

L161L (synonymous)

S287 Frameshift

 

28

 

 

NAT2*12A

803A>G (rs1208)

K268R

Rapid

12,15,17,19,42,43

NAT2*12B

282C>T (rs1041983)
803A>G (rs1208)

Y94Y (synonymous)

K268R

Rapid

9,10,19,25

NAT2*12C

481C>T (rs1799929)
803A>G (rs1208)

L161L (synonymous)

K268R

Rapid

9,10,21,24,25,43

NAT2*12D

364G>A (rs4986996)
803A>G (rs1208)

D122N
K268R

Slow

16

NAT2*12E

282C>T (rs1041983)
578C>T (rs79050330)

803A>G (rs1208)

Y94Y (synonymous)

T193M

K268R

 

30,31,33

NAT2*12F

622T>C (rs56387565)

803A>G (rs1208)

Y208H

K268R

 

30,33

NAT2*12G

609G>T (rs45618543)

803A>G (rs1208)

E203D

K268R

 

31

NAT2*12H

403C>G (rs12720065)

803A>G (rs1208)

L135V

K268R

 

32

NAT2*12I

228C>T (rs72466459)

803A>G (rs1208)

Y76Y (synonymous)

K268R

 

33

NAT2*12J

29T>C (rs72466456)

803A>G (rs1208)

I10T

K268R

 

33

NAT2*12Kf

472A>C (rs139351995)

803A>G (rs1208)

I158L

K268R

 

40

NAT2*12Lf

665T>G

803A>G (rs1208)

F222C

K268R

 

40

NAT2*12Mf

282C>T (rs1041983)

481C>T (rs1799929)

803A>G (rs1208)

Y94Y (synonymous)

L161L (synonymous)

K268R

 

35

NAT2*12Nf

121A>T (rs149283608)

803A>G (rs1208)

N41Y

K268R

 

60

NAT2*12Of

29T>C (rs72466456)

609G>T (rs45618543)

803A>G (rs1208)

I10T

E203D

K268R

 

60

NAT2*12Pf

472A>C (rs139351995)

481C>T (rs1799929)

803A>G (rs1208)

I158L

L161L (synonymous)

K268R

 

60

 

NAT2*13A

282C>T (rs1041983)

Y94Y (synonymous)

Rapid

9,10,12-15, 17,19,22,23,43,44

NAT2*13B

282C>T (rs1041983)

578C>T (rs79050330)

Y94Y (synonymous)

T193M

 

31

NAT2*13Cf

282C>T (rs1041983)

665T>G

Y94Y (synonymous)

F222C

 

40

NAT2*13Df

282C>T (rs1041983)

766A>G (rs55700793)

Y94Y (synonymous)

K256E

 

60

NAT2*13Ef

282C>T (rs1041983)

641C>T

Y94Y (synonymous)

T214I

 

60

NAT2*13Ff

282C>T (rs1041983)

838G>A (rs56393504)

Y94Y (synonymous)

V280M

 

60

NAT2*13Gf

282C>T (rs1041983)

472A>C (rs139351995)

Y94Y (synonymous)

I158L

 

60

 

NAT2*14A

191G>A (rs1801279)

R64Q

Slow

9,10,12-15,17,21,45

NAT2*14B

191G>A (rs1801279)
282C>T (rs1041983)

R64Q

Y94Y (synonymous)

Slow

45,46

NAT2*14C

191G>A (rs1801279)
341T>C (rs1801280)
481C>T (rs1799929)
803A>G (rs1208)

R64Q
I114T
L161L (synonymous)

K268R

Slow

23-25,33

NAT2*14D

191G>A (rs1801279)
282C>T (rs1041983)
590G>A (rs1799930)

R64Q
Y94Y (synonymous)

R197Q

Slow

23,25,36

NAT2*14E

191G>A (rs1801279)
803A>G (rs1208)

R64Q
K268R

Slow

23,31,36

NAT2*14F

191G>A (rs1801279)
341T>C (rs1801280) 
803A>G (rs1208)

R64Q
I114T
K268R

Slow

25

NAT2*14G

191G>A (rs1801279)
282C>T (rs1041983)
803A>G (rs1208)

R64Q
Y94Y (synonymous)

K268R

Slow

26

NAT2*14H

191G>A (rs1801279)
282C>T (rs1041983)

683C>T (rs45518335)

R64Q
Y94Y (synonymous)

P228L

 

31

NAT2*14I

 

191G>A (rs1801279)
481C>T (rs1799929)

803A>G (rs1208)

R64Q
L161L (synonymous)

K268R

 

47

NAT2*14Jf

191G>A (rs1801279)

282C>T (rs1041983)

633G>A

R64Q

Y94Y (synonymous)

T211T (synonymous)

 

40

NAT2*14Kf

191G>A (rs1801279)

282C>T (rs1041983)

838G>A (rs56393504)

R64Q

Y94Y (synonymous)

V280M

 

60

NAT2*14Lf

7A>G (rs200893121)

191G>A (rs1801279)

282C>T (rs1041983)

I3V

R64Q

Y94Y (synonymous)

 

60

 

NAT2*17

434A>C (rs72554616)

Q145P

Slow

9,10,12,15,48

NAT2*18

845A>C (rs56054745)

K282T

Rapid

9,10,12,15,48

NAT2*19

190C>T (rs1805158)

R64W

Slow

49-51

NAT2*20

600A>G (rs72466461)

E200E (synonymous)

 

33

NAT2*21

458C>T (rs72466460)

T153I

 

33

NAT2*22f

609G>T (rs45618543)

E203D

 

40

NAT2*23f

70T>A (rs45477599)

L24I

 

40

NAT2*24f

403C>G (rs12720065)

L135V

 

40

NAT2*25f

665T>G

F222C

 

40

NAT2*26f

809T>C

I270T

 

60

NAT2*27f

589C>T

R197Stop

 

60

 

 

Footnotes

 

(a) Human NAT2 alleles should be written in upper case and italicized. Protein products of the alleles are also upper case but not italicized and the asterisk is omitted (or replaced by underscore). For example, the allele NAT2*4 encodes the protein NAT2 4 (or NAT2_4).

 

(b) Reference gene sequence (NAT2*4) is published in Genbank Assession Number X14672. NAT2*4 has historically been designated "wildtype". Since it is the most common occurring allele in some but not all ethnic groups, the designation of "wildtype" allele is somewhat arbitrary and is dependent upon the ethnicity of the population studied.

 

(c) Signature SNP for each cluster is shown in red font. SNPs should be identified by designating "A" of the ATG translation initiation codon as number 1. SNPs upstream of this site are designated by negative numbers and SNPs downstream of this site are designated by positive numbers [58].

 

(d) Phenotype assignments reflect most current research but are not necessarily a consensus of all research papers. Evidence also exists for heterogeneity within the slow acetylator phenotype. For comprehensive reviews, see references [52-56]. Although additional SNPs have been identified outside the open reading frame (e.g., see refs [31,32,57]), they will not be named until a functional effect is observed.

 

(e) The SNPs on NAT2*5J were determined by RFLP methods which are indirect.

 

(f) Haplotypes predicted from genotypes by computational PHASE analysis.

 

 

For new submissions or enquiries, please contact Dr. Sotiria Boukouvala (sboukouv@mbg.duth.gr).

 

 

Literature

 

[1]              Deguchi, T. Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver. J. Biol. Chem. 267: 18140-18147, 1992.

[2]              Blum, M., Demierre, A., Grant, D.M., Heim, M. and Meyer, U.A. Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proc. Natl. Acad. Sci. USA 88: 5237-5241, 1991.

[3]              Vatsis, K.P., Martell, K.J. and Weber, W.W. Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proc. Natl. Acad. Sci. USA 88: 6333-6337, 1991.

[4]              Blum, M., Grant, D.M., McBride, W., Heim, M. and Meyer, U.A. Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Biol. 9: 193-203, 1990.

[5]              Ebisawa, T. and Deguchi. T. Structure and restriction fragment length polymorphism of genes for human liver arylamine N-acetyltransferases. Biochem. Biophys. Res. Commun. 177: 1252-1257, 1991.

[6]              Ohsako, S. and Deguchi, T. Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver. J. Biol. Chem. 265: 4630-4634, 1990.

[7]              Grant, D.M., Blum, M., Demierre, A. and Meyer, U.A. Nucleotide sequence of an intronless gene for a human arylamine N-acetyltransferase related to polymorphic drug acetylation. Nucleic Acids Res. 17: 3978, 1989.

[8]              Hickman, D. and Sim, E. N-Acetyltransferase polymorphism: Comparison of phenotype and genotype in humans. Biochem. Pharmacol. 42: 1007-1014, 1992.

[9]              Hein, D.W., Ferguson, R.J., Doll, M.A., Rustan, T.D. and Gray, K. Molecular genetics of human polymorphic N-acetyltransferase: enzymatic analysis of 15 recombinant human wild-type, mutant, and chimeric NAT2 allozymes. Hum. Mol. Genet. 3: 729-734, 1994.

[10]         Hein, D.W., Doll, M.A., Rustan, T.D. and Ferguson, R.J. Metabolic activation of N-hydroxyarylamines and N-hydroxyarylamides by 16 recombinant human NAT2 allozymes: Effects of 7 specific NAT2 nucleic acid substitutions. Cancer Res. 55: 3531-3536, 1995.

[11]         Hickman, D., Palamanda, J.R., Unadkat, J.D. and Sim, E. Enzyme kinetic properties of human recombinant arylamine N-acetyltransferase 2 allotypic variants expressed in Escherichia Coli. Biochem. Pharmacol. 50: 697-703, 1995.

[12]         Fretland, A.J., Leff, M.A., Doll, M.A. and Hein, D.W. Functional characterization of human N-acetyltransferase 2 (NAT2) single nucleotide polymorphisms. Pharmacogenetics 11: 207-215, 2001.

[13]         Svensson, C.K. and Hein, D.W. Phenotypic and genotypic characterization of N-acetylation. In: Drug Metabolism and Transport: Molecular Methods and Mechanisms. L.H. Lash, Editor, Methods in Pharmacology and Toxicology Series, The Humana Press, Totowa, NJ, pp. 173-195, 2005.

[14]         Hein, D.W. N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene 25: 1649-1658, 2006.

[15]         Hein, D.W., Fretland, A.J. and Doll, M.A. Effects of single nucleotide polymorphisms in human N-acetyltransferase 2 on metabolic activation (O-acetylation) of heterocyclic amine carcinogens. Int. J. Cancer 119: 1208-1211, 2006.

[16]         Zang, Y., Zhao, S., Doll, M.A., States, J.C. and Hein, D.W. Functional characterization of the A411T (L137F) and G364A (D122N) genetic polymorphisms in human N-acetyltransferase 2. Pharmacogenet. Genomics 17: 37-45, 2007.

[17]         Zang, Y., Doll, M.A., Zhao, S., States, J.C. and Hein, D.W. Functional characterization of single nucleotide polymorphisms and haplotypes of human N-acetyltransferase 2. Carcinogenesis 28: 1665-1671, 2007.

[18]         Hickman, D., Risch, A., Camilleri, J.P. and Sim, E. Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants. Pharmacogenetics 2: 217-226, 1992.

[19]         Lin, J.J., Han, C.Y., Lin B.K., and Hardy, S. Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, Blacks, Hispanics, and Whites: application to metabolic epidemiology. Am. J. Hum. Genet. 52: 827-834, 1993.

[20]         Abe, M., Deguchi, T. and Suzuki, T. The structure and characteristics of a fourth allele of polymorphic N-acetyltransferase gene found in the Japanese population. Biochem. Biophys. Res. Comm. 191: 811-816, 1993.

[21]         Ferguson, R.J., Doll, M.A., Rustan, T.D., Gray, K. and Hein, D.W. Cloning, expression, and functional characterization of two mutant (NAT2 191 and NAT2 341/803) and wild-type human polymorphic N-acetyltransferase (NAT2) alleles. Drug Metab. Dispos. 22: 371-376, 1994.

[22]         Cascorbi, I., Drakoulis, N., Brockmoller, J., Mauer, A., Sperling, K. and Roots, I. Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. Am. J. Hum. Genet. 57: 581-592, 1995.

[23]         Martinez, C., Agundez, J.A.G., Olivera, M., Martin, R., Ladero, J.M. and Benitez, J. Lung cancer and mutations at the polymorphic NAT2 gene locus. Pharmacogenetics 5: 207-214, 1995.

[24]         Agundez, J.A.G., Olivera, M., Ladero, J.M., Lescure-Rodriguez, A., Ledesma, M.C., Diaz-Rubio, M., Meyer, U.A. and Benitez, J. Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. Pharmacogenetics 6: 501-512, 1996.

[25]         Agundez, J.A.G., Olivera, M., Martinez, C., Ladero, J.M. and Benitez, J. Identification and prevalence study of 17 allelic variants of the human NAT2 gene in a white population. Pharmacogenetics 6: 423-428, 1996.

[26]         Leff, M.A., Fretland, A.J., Doll, M.A. and Hein, D.W. Novel human N-acetyltransferase 2 alleles that differ in mechanism for slow acetylator phenotype. J. Biol. Chem. 274: 34519-34522, 1999.

[27]         Woolhouse, N.M., Qureshi, M.M. and Bayoumi, R.A. A new mutation C759T in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics 7: 83-84, 1997.

[28]         Anitha, A. and Banerjee, M. Arylamine N-acetyltransferase 2 polymorphism in the ethnic populations of South India. Int. J. Mol. Med. 11: 125-131, 2003.

[29]         Tanira, M.O.M., Simsek, M., Al Balushi, K., Al Lawatia, K., Al Barawani, H. and Bayoumi, R.A. Distribution of arylamine N-acetyltransferase 2 (NAT2) genotypes among Omani Arabs. SQU J. Sci. Res.: Med. Sci. 5: 9-14, 2003.

[30]         Patin, E., Barreiro, L.B., Sabeti, P.C., Austerlitz, F., Luca, F., Sajantila, A., Behar, D.M., Semino, O., Sakuntabhai, A., Guiso, N., Gicquel, B., McElreavey, K., Harding, R.M., Heyer, E. and Quintana-Murci, L. Deciphering the ancient and complex evolutionary history of human N-acetyltransferase genes. Am. J. Hum. Genet. 78: 423-436, 2006.

[31]         Patin, E., Harmant, C., Kidd, K.K., Kidd, J., Froment, A., Mehdi, S.Q., Sica, L., Heyer, E. and Qinatan-Murci, L. Sub-Saharan African coding sequence variation and haplotype diversity at the NAT2 gene. Hum. Mutat. 27: 720, 2006.

[32]         Sabbagh, A., Langaney, A., Darlu, P., Gerard, N., Krishnamoorthy, R. and Poloni, E.S. Worldwide distribution of NAT2 diversity: implications for NAT2 evolutionary history. BMC Genet. 9: 21, 2008.

[33]         Teixeira, R.L.F., Silva Jr, F.P., Silveira, A.R., Cabello, P.H., Mendonca-Lima, L., Rabahi, M.F., Kritski, A.L., Mello, F.C.Q., Suffys, P.N., Miranda, A.B. and Santos, A.R. Sequence analysis of NAT2 gene in Brazilians: identification of undescribed single nucleotide polymorphisms and molecular modeling of the N-acetyltransferase 2 protein structure. Mut. Res. 683: 43-49, 2010.

[34]         Chauhan, N. and Padh, H. Variants of NAT2 polymorphisms: Intra and inter-ethnic differences. African J. Biotechnol. 13: 4639-4646, 2014.

[35]         Naazneen Khan (India), unpublished haplotypes predicted by computational PHASE analysis.

[36]         Hein, D.W. and Doll, M.A. Enzymatic characterization of novel human NAT2 alleles. Fourth International Workshop on the Arylamine N-acetyltransferases, Alexandroupolis, Greece, September 2007.

[37]         Dandara, C., Masimirembwa, C.M., Magimba, A., Kaaya, S., Sayi, J., Sommers, D.K., Snyman, J.R. and Hasler, J.A. Arylamine N-acetyltransferase (NAT2) genotypes in Africans: the identification of a new allele with nucleotide changes 481C>T and 590G>A. Pharmacogenetics 13: 55-58, 2003.

[38]         Matimba, A., Del-Favero, J., Van Broeckhoven, C. and Masimirembwa, C. Novel variants of major drug metabolizing enzyme genes in diverse African populations and their predicted functional effects. Hum. Genom. 3: 169-190, 2009.

[39]         Teixeira, R.L., Morato, R.G., Cabello, P.H., Muniz, L.M.K., Moreira, A.S.R., Kritski, A.L., Mello, F.C.Q., Suffys, P.N., Miranda, A.B. and Santos, A.R. Genetic polymorphisms of NAT2, CYP2E1, GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients. Mem. Inst. Oswaldo Cruz 106: 716-724, 2011.

[40]         Mortensen, H.M., Froment, A., Lema, G., Bodo, J.M., Ibrahim, M., Nyambo, T.B., Omar, S.A., Tishkoff, S.A. Characterization of genetic variation and natural selection at the arylamine N-acetyltransferase genes in global human populations. Pharmacogenomics 12:1545-1558, 2011.

[41]         Sekine, A., Saito, S., Iida, A., Mitsunobu, Y., Higuchi, S., Harigae, S. and Nakamura, Y. Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1, and L1CAM in the Japanese population. J. Hum. Genet. 46: 314-319, 2001.

[42]         Cascorbi, I., Brockmoller, J., Bauer, S., Reum, T. and Roots, I. NAT2*12A (803A-G) codes for rapid arylamine N-acetylation in humans. Pharmacogenetics 6: 257-259, 1996.

[43]         Bolt, H.M., Selinski, S., Dannappel, D., Blaszkewicz, M. and Golka, K. Re-investigation of the concordance of human NAT2 phenotypes and genotypes. Arch. Toxicol. 79: 196-200, 2005.

[44]         Agundez, J.A., Martinez, C., Olivera, M., Ledesma, M.C., Ladero, J.M. and Benitez, J. Molecular analysis of the arylamine N-acetyltransferase polymorphism in a Spanish population. Clin. Pharmacol. Ther. 56: 202-209, 1994.

[45]         Bell, D.A., Taylor, J.A., Butler, M.A., Stephens, E.A., Wiest, J., Brubaker, L.H., Kadlubar, F.F. and Lucier, G.W. Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. Carcinogenesis 14: 1689-1692, 1993.

[46]         Delomenie, C., Sica, L., Grant, D.M., Krishnamoorthy, R. and Dupret, J.M. Genotyping of the polymorphic N-acetyltransferase (NAT2*) gene locus in two native African populations. Pharmacogenetics 6: 177-185, 1996.

[47]         Agundez, J., Golka, K., Martinez, C., Selinski, S., Blaszkewicz, M. and Garcia-Martin, E. Unraveling ambiguous NAT2 genotyping data. Clin.Chem. 54: 1390-1394, 2008.

[48]         Lin, H.J., Han, C.Y., Lin, B.K. and Hardy, S. Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene. Pharmacogenetics 4: 125-134, 1994.

[49]         Shishikura, K., Hohjoh, H. and Tokunaga, K. Novel allele containing 190C>T nonsynonymous substitution in the N-acetyltransferase (NAT2) gene. Hum. Mut. 15: 581, 2000.

[50]         Lee, S.Y., Lee, K.A., Ki, C.S., Kwon, O.J., Kim, H.J., Chung, M.P., Suh, G.Y. and Kim, J.W. Complete sequencing of a genetic polymorphism in NAT2 in the Korean population. Clin. Chem. 48: 775-777, 2002.

[51]         Zhu, Y., Doll, M.A. and Hein, D.W. Functional genomics of C190T single nucleotide polymorphism in human N-acetyltransferase 2. Biol. Chem. 383: 983-987, 2002.

[52]         Grant, D.M., Hughes, N.C., Janezic, S.A., Goodfellow, G.H., Chen, H.J., Gaedigk, A., Yu, V.L. and Grewal, R. Human acetyltransferase polymorphisms. Mutat. Res. 376: 61-70, 1997.

[53]         Butcher, N.J., Boukouvala, S., Sim, E. and Minchin, R.F. Pharmacogenetics of the arylamine N-acetyltransferases. Pharmacogenomics J. 2: 30-42, 2002.

[54]         Hein, D.W. Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mut. Res. 506-507: 65-77, 2002.

[55]         Boukouvala, S. and Fakis, G. Arylamine N-acetyltransferases: What we learn from genes and genomes. Drug Metab. Rev. 37: 511-564, 2005.

[56]         Sim, E., Westwood, I. and Fullam, E. Arylamine N-acetyltransferases. Expert Opin. Drug Metab. Toxicol. 3: 169-184, 2007.

[57]         Yuliwulandari, R., Sachrowardi, Q., Nishida, N., Takasu, M., Batubara, L., Susmiarsih, T.P., Rochani, J.T., Wikaningrum, R., Miyashita, R., Miyagawa, T., Sofro, A.S., Tokunaga, K. Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature. J. Hum. Genet. 53: 201-209, 2008.

[58]         Hein, D.W., Boukouvala, S., Grant, D.M., Minchin, R.F. and Sim, E. Changes in consensus arylamine N-acetyltransferase (NAT) gene nomenclature. Pharmacogenet. Genom. 18: 367-368, 2008.

[59]         Dr. Lilly Verhagen (Netherlands), unpublished data (SNP found in two tuberculosis patients from Venezuela).

[60]         Podgorn, E., Diallo, I., Vangenot, C., Sanchez-Mazas, A., Sabbagh, A., Čern, V., Poloni, E.S. Variation in NAT2 acetylation phenotypes is associated with differences in food-producing subsistence modes and ecoregions in Africa. BMC Evol. Biol. 15:263 (2015).