Association of N-acetyl transferase 2 gene polymorphism and slow acetylator phenotype with young onset and late onset Parkinson's disease among Indians.
OBJECTIVE
To investigate the association of (i) seven SNPs and SNP haplotypes in the phase II conjugating enzyme N-acetyl transferase 2 gene; and (ii) slow acetylator phenotype, with the development of young onset (YO) and late onset (LO) Parkinson's disease (PD) among Indians.


METHODS
A total of 267 cases (132 YOPD, age at onset < or =40 years; 135 LOPD, age at onset >40 years) and 324 age and sex matched controls (132 for YOPD and 192 for LOPD) were genotyped for NAT2 SNPs. Allelic, genotypic and haplotypic association was tested by chi2 using a case-control approach. Chi2 test of association of acetylation phenotype (by genotype) with PD was also carried out.


RESULTS
Of the seven SNPs genotyped, SNP191 was monomorphic and therefore, not included for analysis. With SNPs 590 and 857 a significant allelic [OR (95% CI) 4.147 (2.28-7.54) for A allele and 2.565 (1.34-4.92) for A allele, respectively] and genotypic [OR (95% CI) 0.27 (0.14-0.52) for GG and 0.35 (0.174-0.712) for GG, respectively] association with YOPD was observed. There was a significant allelic and genotypic association of SNP 282 with LOPD [chi2 = 8.92, P = 0.003 and chi2 = 10.2, P = 0.006, respectively]. There was also a significant association of protective and predisposing haplotypes TCGG and TCAG [OR (95% CI) 0.446 (0.31-0.63) and 3.742 (2.0-6.99), respectively] with YOPD and predisposing haplotype TCGA [OR (95% CI) 3.214 (1.43-7.22)] with LOPD. Slow acetylator phenotype was significantly associated with YOPD [OR (95% CI) 2.32 (1.2-4.48)].


CONCLUSIONS
Specific SNPs and SNP haplotypes in NAT2 and slow acetylator phenotype are significantly associated with YOPD and to a lesser extent with LOPD among Indians.
Chaudhary
Shashi
S
Department of Genetics, University of Delhi South Campus, New Delhi, India.
Behari
Madhuri
M
Dihana
Maninder
M
Swaminath
Pazhayannur V
PV
Govindappa
Shyla T
ST
Jayaram
Sachi
S
Singh
Sumit
S
Muthane
Uday B
UB
Juyal
Ramesh C
RC
B K
Thelma
T
D000107:Acetylation; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human