A poly(ADP-ribose) polymerase haplotype spanning the promoter region confers susceptibility to rheumatoid arthritis.

Abstract

OBJECTIVE:

To investigate the association of the poly(ADP-ribose) polymerase 1 (PARP-1) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition.

METHODS:

An association study with 213 Spanish RA patients and 242 healthy subjects was carried out to investigate the association of all known PARP-1 gene promoter polymorphisms, i.e., a CA microsatellite repeat, a poly(A)(n), and 3 single point mutations (C410T, C1362T, and G1672A), with disease susceptibility. Additionally, we analyzed the distribution of PARP-1 polymorphisms in 58 Spanish families with 1 or more affected members.

RESULTS:

Upon complete genotyping of the panel of 455 samples, strong linkage disequilibrium was observed among the 5 PARP-1 polymorphisms. Only 2 PARP-1 haplotypes were detected: haplotype A (410T-[A](10)-[CA](10-12)-1362C, which includes short PARP-1 CA alleles) and haplotype B (410C-[A](11)-[CA](13-20)-1362T, always paired with long PARP-1 CA variants). Regarding the G1672A variation, although linkage disequilibrium was detected, it did not seem to be part of the conserved haplotypes described. Haplotype B was statistically overrepresented in the RA patient group compared with the healthy subjects (odds ratio 1.42, 95% confidence interval 1.06-1.91, P = 0.019). In addition, a significant dose effect of PARP-1 haplotype carriage on disease predisposition was observed. Of note, within haplotype B, the PARP-1 CA 97-bp allele was found to be the RA-predisposing marker (odds ratio 2.17, 95% confidence interval 1.27-3.72, P = 0.003, corrected P < 0.05).

CONCLUSION:

Our results demonstrate the existence of 2 unique PARP-1 haplotypes in the Spanish population and provide the first evidence that PARP-1 haplotypes play a role in susceptibility to RA.

• Authors: M Pascual, M A López-Nevot, R Cáliz, M A Ferrer, A Balsa, D Pascual-Salcedo, J Martín
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 48 Issue 3 Pg. 638-41 (Mar 2003) ISSN: 0004-3591 [Print] United States
• PMID: 12632415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Poly(ADP-ribose) Polymerases

Topics

• Arthritis, Rheumatoid (enzymology, epidemiology, genetics)
• DNA Primers (chemistry)
• Female
• Gene Frequency
• Genetic Predisposition to Disease (genetics)
• Haplotypes
• Humans
• Male
• Microsatellite Repeats
• Molecular Epidemiology
• Poly(ADP-ribose) Polymerases (genetics)
• Polymorphism, Genetic
• Promoter Regions, Genetic (genetics)
• Spain (epidemiology)