Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus.
OBJECTIVE
The objective of this study was to confirm whether polymorphisms of the poly(ADP-ribose) polymerase gene (PARP) are associated with genetic susceptibility to systemic lupus erythematosus (SLE) and to investigate the possible association of nephritis and arthritis in SLE with PARP polymorphisms.


METHODS
Using direct DNA sequencing in 24 individuals, we identified 44 sequence variants within exons and their flanking regions, including the 1.5-kb promoter region of PARP. Six common polymorphic sites were selected for larger-scale genotyping (in 350 Korean SLE patients and 330 healthy controls), which identified six common haplotypes.


RESULTS
Although no statistically significant association with the risk of SLE was observed, we found that two single-nucleotide polymorphisms (SNPs -1963A --> G and +28077G --> A) were significantly associated with an increased risk of nephritis, and one non-synonymous variant [+40329T --> C(V762A)] was also significantly associated with an increased risk of arthritis, while the -1963A --> G SNP showed a protective effect on arthritis in Korean SLE patients.


CONCLUSIONS
Our results demonstrate that PARP polymorphisms are not associated with SLE susceptibility, but that -1963A --> G, +28077G --> A and +40329T --> C(V762A) are significantly associated with nephritis and arthritis in Korean SLE patients.
Hur
J-W
JW
Department of Internal Medicine, Hospital for Rheumatic Diseases, Hanyang University, Seoul, Republic of Korea.
Sung
Y-K
YK
Shin
H D
HD
Park
B L
BL
Cheong
H S
HS
Bae
S-C
SC
D000293:Adolescent; D000328:Adult; D000368:Aged; D001168:Arthritis / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D011065:Poly(ADP-ribose) Polymerases