Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus
Poly(ADP-ribose) polymerase (PARP) polymorphisms associated with nephritis and arthritis in systemic lupus erythematosus
复制标题
DOI：
10.1093/rheumatology/kei262
复制
发表时间：
2006-06-01
期刊：
影响因子：
5.5
通讯作者：
Bae, S. -C.
中科院分区：
文献类型：
--
作者：
Hur, J. -W.;Sung, Y. -K.;Bae, S. -C.
Objective.本研究的目的是证实聚腺苷二磷酸核糖聚合酶基因（PARP）多态性是否与系统性红斑狼疮（SLE）的遗传易感性相关，并探讨PARP多态性与SLE肾炎和关节炎的可能关联。使用直接DNA测序在24个人，我们确定了44个外显子及其侧翼区，包括1.5 kb的启动子区的PARP序列变异。选择6个常见多态位点进行大规模基因分型（在350名韩国SLE患者和330名健康对照中），确定6个常见单倍型。虽然没有观察到与SLE风险的统计学显著相关性，但我们发现两个单核苷酸多态性与SLE风险相关。（SNPs -1963 A-> G和+28077 G-> A）与肾炎风险增加显著相关，一个非同义变体[+40329 T-> C（V762 A）]也与关节炎风险增加显著相关，而-1963A G SNP对韩国SLE患者关节炎有保护作用。我们的研究结果表明PARP多态性与SLE易感性无关，但-1963A-> G，+28077G -> A和+40329T -> C（V762 A）与韩国SLE患者的肾炎和关节炎显著相关。
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.Conclusion. 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.