Hur Jin-Wuk, Sung Yoon-Kyoung, Shin Hyoung Doo, Park Byung Lae, Cheong Hyun Sub, Bae Sang-Cheol
Division of Rheumatology, Department of Internal Medicine, Eulji University College of Medicine, Seoul, Republic of Korea.
Rheumatol Int. 2008 Jun;28(8):783-9. doi: 10.1007/s00296-007-0509-0. Epub 2007 Dec 19.
Three-prime repair exonucleases 1 and 2 (TREX1 and TREX2) play a role in the metabolism and clearance of DNA. The objective of this study was to confirm whether polymorphisms of TREX1 and TREX2 are associated with genetic susceptibility to systemic lupus erythematosus (SLE), and examine associations with autoantibodies (auto-Abs) in SLE. We investigated the genetic variants in 24 Korean individuals by direct sequencing. The genotype distributions of single-nucleotide polymorphisms (SNPs) and haplotypes were analyzed with multiple logistic regression models while controlling for covariates. We identified 12 and 5 SNPs of TREX1 and TREX2, of which -20260G>C, -389T>C, -381C>T, and +531C>T SNPs of TREX1; -23386G>C, -14703G>A, -7279C>T, and +1747C>T SNPs of TREX2; and each of three haplotypes were selected for larger scale genotyping (n = 1,053). No statistically significant association with the risk of SLE was observed in TREX1 and TREX2. TREX1 polymorphism -20260G>C showed protective effect on the production of anti-Ro Ab, and +531C>T in exon 16 and ht2 [G-T-C-T] showed also protective effect on the production of anti-dsDNA Ab, although the effect of +531C>T disappeared after multiple correction.
3'-修复核酸外切酶1和2（TREX1和TREX2）在DNA的代谢和清除中发挥作用。本研究的目的是确认TREX1和TREX2的多态性是否与系统性红斑狼疮（SLE）的遗传易感性相关，并研究其与SLE自身抗体（自身抗体）的关联。我们通过直接测序调查了24名韩国个体的基因变异。在控制协变量的同时，使用多元逻辑回归模型分析单核苷酸多态性（SNP）和单倍型的基因型分布。我们鉴定出TREX1和TREX2的12个和5个SNP，其中TREX1的-20260G>C、-389T>C、-381C>T和+531C>T SNP；TREX2的-23386G>C、-14703G>A、-7279C>T和+1747C>T SNP；以及三种单倍型中的每一种都被选择用于更大规模的基因分型（n = 1,053）。在TREX1和TREX2中未观察到与SLE风险有统计学意义的关联。TREX1多态性-20260G>C对抗Ro抗体的产生具有保护作用，外显子16中的+531C>T和单倍型ht2 [G-T-C-T]对抗双链DNA抗体的产生也具有保护作用，尽管在多重校正后+531C>T的作用消失。
