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南非印第安人和高加索银屑病关节炎患者中 miR-146a G/C rs2910164 变异。

MiR-146a G/C rs2910164 variation in South African Indian and Caucasian patients with psoriatic arthritis.

机构信息

Department of Internal Medicine, Prince Mshiyeni Memorial Hospital and School of Clinical Medicine, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.

Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.

出版信息

BMC Med Genet. 2018 Mar 27;19(1):48. doi: 10.1186/s12881-018-0565-1.

Abstract

BACKGROUND

Psoriasis and psoriatic arthritis (PsA) are inflammatory associated autoimmune disorders. MicroRNA (miR)-146a plays a crucial role in regulating inflammation. A single nucleotide polymorphism in the miR-146a gene (rs2910164), aberrantly alters its gene expression and linked with the pathogenesis of several disorders, including psoriasis and PsA. In South Africa, psoriasis and PsA are extremely rare in the indigenous African population and most common in both the Indian and Caucasian population. The aim of this study was to investigate whether the miR-146a rs2910164 contributes towards psoriasis and PsA development in South African Indian and Caucasian patients.

METHODS

South African Indian (n = 84) and Caucasian (n = 32) PsA patients (total n = 116) and healthy control subjects (Indian: n = 62 and Caucasian: n = 38; total n = 100) were recruited in the study. DNA was extracted from whole blood taken from all subjects, and genotyped for the miR-146a rs2910164 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data for laboratory parameters were obtained from pathology reports. The consulting rheumatologist collected all other clinical data.

RESULTS

Unstratified data (Caucasians + Indians): A significant decrease in C-reactive protein (CRP) levels in PsA patients was observed (CRP monitored at inclusion vs. after 6 months of treatment) (18.95 ± 2.81 mg/L vs. 9.68 ± 1.32 mg/L, p = 0.0011). The miR-146a rs2910164 variant C-allele frequency in PsA patients was significantly higher vs. healthy controls (35.78% vs. 26% respectively, p = 0.0295, OR = 1.59 95% CI 1.05-2.40). Stratified data (Indians): The variant C-allele frequency in Indian PsA patients was significantly higher vs. healthy Indian controls (35.71% vs. 22.58%, p = 0.0200, OR = 1.91 95% CI 1.13-3.22). Stratified data (Caucasians): The variant C-allele frequency distribution between Caucasian PsA patients and healthy Caucasian controls was similar.

CONCLUSION

The rs2910164 variant C-allele may play a role in the progression of PsA in the South African Indian population. The main limitation in this study was the small sample size in the case-control cohorts, with a low overall statistical power (post-hoc power analysis = 19%).

摘要

背景

银屑病和银屑病关节炎(PsA)是与炎症相关的自身免疫性疾病。微小 RNA(miR)-146a 在调节炎症中起着至关重要的作用。miR-146a 基因中的单核苷酸多态性(rs2910164)改变了其基因表达,与包括银屑病和 PsA 在内的几种疾病的发病机制有关。在南非,银屑病和 PsA 在土着非洲人群中极为罕见,而在印度人和高加索人群中最为常见。本研究旨在探讨 miR-146a rs2910164 是否有助于南非印度人和高加索人银屑病和 PsA 的发病。

方法

纳入了南非印度人(n=84)和高加索人(n=32)PsA 患者(共 n=116)和健康对照者(印度人:n=62;高加索人:n=38;共 n=100)。从所有受试者的全血中提取 DNA,并使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对 miR-146a rs2910164 进行基因分型。实验室参数数据来自病理报告。咨询风湿病学家收集了所有其他临床数据。

结果

未分层数据(高加索人+印度人):观察到 PsA 患者的 C 反应蛋白(CRP)水平显著下降(在纳入时与治疗后 6 个月监测 CRP)(18.95±2.81mg/L 比 9.68±1.32mg/L,p=0.0011)。PsA 患者的 miR-146a rs2910164 变体 C-等位基因频率明显高于健康对照组(分别为 35.78%和 26%,p=0.0295,OR=1.59,95%CI,1.05-2.40)。分层数据(印度人):印度人 PsA 患者的变体 C-等位基因频率明显高于印度健康对照组(35.71%比 22.58%,p=0.0200,OR=1.91,95%CI,1.13-3.22)。分层数据(高加索人):高加索人 PsA 患者和健康高加索对照组之间的变体 C-等位基因频率分布相似。

结论

rs2910164 变体 C-等位基因可能在南非印度人群中 PsA 的进展中起作用。本研究的主要局限性是病例对照队列的样本量较小,整体统计效力较低(事后功效分析=19%)。

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