Kim Tae-Ho, Bae Sang-Cheol, Lee Sang-Han, Kim Shin-Yoon, Baek Seung-Hoon
Biomedical Research Institute, Kyungpook National University Hospital, 135 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea; Skeletal Diseases Genome Research Center, Kyungpook National University, 135 Dongdeok-ro, Jung-gu, Daegu 700-721, Republic of Korea.
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 17 Haengdang-Dong, Seongdong-Gu, Seoul 133-792, Republic of Korea.
Biomed Res Int. 2016;2016:9208035. doi: 10.1155/2016/9208035. Epub 2016 Jun 30.
Osteonecrosis of the femoral head (ONFH) is a complex and multifactorial disease that is influenced by a number of genetic factors in addition to environmental factors. Some autoimmune disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are associated with the development of ONFH. Complement receptor type 2 (CR2) is membrane glycoprotein which binds C3 degradation products generated during complement activation. CR2 has many important functions in normal immunity and is assumed to play a role in the development of autoimmune disease. We investigated whether CR2 gene polymorphisms are associated with risk of ONFH in SLE patients. Eight polymorphisms in the CR2 gene were genotyped using TaqMan™ assays in 150 SLE patients and 50 ONFH in SLE patients (SLE_ONFH). The association analysis of genotyped SNPs and haplotypes was performed with ONFH. It was found that three SNPs, rs3813946 in 5'-UTR (untranslated region), rs311306 in intron 1, and rs17615 in exon 10 (nonsynonymous SNP; G/A, Ser639Asn) of the CR2 gene, were associated with an increased risk of ONFH under recessive model (P values; 0.0040.016). Haplotypes were also associated with an increased risk (OR; 3.73) of ONFH in SLE patients. These findings may provide evidences that CR2 contributes to human ONFH susceptibility in Korean SLE patients.
股骨头坏死（ONFH）是一种复杂的多因素疾病，除环境因素外，还受多种遗传因素影响。一些自身免疫性疾病，包括系统性红斑狼疮（SLE）、类风湿性关节炎（RA）和炎症性肠病（IBD），与ONFH的发生有关。补体受体2型（CR2）是一种膜糖蛋白，可结合补体激活过程中产生的C3降解产物。CR2在正常免疫中具有许多重要功能，并被认为在自身免疫性疾病的发生中起作用。我们研究了CR2基因多态性是否与SLE患者发生ONFH的风险相关。使用TaqMan™分析对150例SLE患者和50例SLE合并ONFH患者（SLE_ONFH）的CR2基因中的8个多态性进行基因分型。对基因分型的单核苷酸多态性（SNP）和单倍型与ONFH进行关联分析。结果发现，CR2基因5'-非翻译区（UTR）的rs3813946、内含子1中的rs311306和外显子10中的rs17615（非同义SNP；G/A，Ser639Asn）这三个SNP在隐性模型下与ONFH风险增加相关（P值为0.0040.016）。单倍型也与SLE患者ONFH风险增加相关（比值比；3.73）。这些发现可能为CR2导致韩国SLE患者易患ONFH提供证据。
