Increased genotype frequency of N-acetyltransferase 2 slow acetylation in patients with rheumatoid arthritis.
OBJECTIVE
Acetylation polymorphism can alter therapeutic responses and toxicity to certain xenobiotics and may also be a factor that influences a patient's susceptibility to certain diseases. We investigated whether patients with rheumatoid arthritis (RA) differed from healthy individuals with regard to genotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2).


METHODS
NAT2 polymorphism was compared in 118 healthy subjects and 82 patients with RA. NAT2 alleles (*4, *5, *6, and *7) were determined by polymerase chain reaction-restriction fragment length polymorphism methods with deoxyribonucleic acid extracted from peripheral blood.


RESULTS
A statistically significant increase in the proportion of homozygous slow acetylators with 2 mutated alleles (84.1%) was found among patients with RA in comparison with healthy subjects (52.5%; P <.0001). The risk of development of RA was almost 5-fold greater in slow acetylators than in fast acetylators (odds ratio, 4.79; 95% confidence interval, 2.28-10.21). There was no correlation between NAT2 polymorphism and presence of rheumatoid factor, extra-articular manifestations, and age at first occurrence of disease symptoms.


CONCLUSIONS
NAT2 slow acetylation genotype may be a risk factor of individual susceptibility to RA.
Pawlik
Andrzej
A
Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Academy of Medicine, Szczecin, Poland. pawand@poczta.onet.pl
Ostanek
Lidia
L
Brzosko
Iwona
I
Gawroska-Szklarz
Barbara
B
Brzosko
Marek
M
Dabrowska-Zamojcin
Ewa
E
D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human