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NEJM:两个与特发性膜性肾病相关基因被发现

来源:科技日报 2011-02-21 09:13

英国布里斯托尔大学2月17日发布新闻公告称,该校科学家领导的一个国际研究小组最新发现了两个与特发性膜性肾病密切相关的基因。公报称,该发现有助于科学家更好地理解特发性膜性肾病病理,从而找到更有效的治疗方法。相关研究成果发表在最新一期的《新英格兰医学杂志》上。

特发性膜性肾病是成年人肾病综合征中最常见的病理类型之一,其病理至今尚不完全清楚。一由欧洲多国科学家组成的研究小组,对来自英国、法国以及荷兰的三组患有特发性膜性肾病的556名白种人进行了单核苷酸多态性全基因组关联研究。通过数据分析发现,位于染色体2q24和染色体6p21两个基因座上的等位基因——PLA2R1和HLA-DQA1,与特发性膜性肾病有密切关联。携有这两个风险等位基因的人,其特发性膜性肾病的发病可能性高达78.5%。

公告称,这一发现将使科学家更好地了解特发性膜性肾病病因,从而更准确地预测该种疾病的遗传易感人群,提高肾脏移植后复发可能性预测的准确率,也有助于最终设计出更合理的治疗方案。

该项目领导者、英国布里斯托大学医学院院长彼得·马蒂逊教授表示,该发现也表明,在人类免疫系统以及自身免疫疾病中,基因扮演着至关重要的角色。(生物谷Bioon.com)

生物谷推荐原文出处:

N Engl J Med 2011; 364:616-626

Risk HLA-DQA1 and PLA2R1 Alleles in Idiopathic Membranous Nephropathy

Horia C. Stanescu, M.D., Mauricio Arcos-Burgos, M.D., Ph.D., Alan Medlar, M.Sc., Detlef Bockenhauer, M.D., Ph.D., Anna Kottgen, M.D., M.P.H., Liviu Dragomirescu, Ph.D., Catalin Voinescu, B.Sc., Naina Patel, B.Sc., Kerra Pearce, M.Sc., Mike Hubank, Ph.D., Henry A.F. Stephens, Ph.D., Valerie Laundy, F.I.M.L.S., Sandosh Padmanabhan, M.D., Ph.D., Anna Zawadzka, Julia M. Hofstra, M.D., Marieke J.H. Coenen, Ph.D., Martin den Heijer, M.D., Ph.D., Lambertus A.L.M. Kiemeney, Ph.D., Delphine Bacq-Daian, M.Sc., Benedicte Stengel, M.D., Ph.D., Stephen H. Powis, Ph.D., F.R.C.P., Paul Brenchley, Ph.D., John Feehally, D.M., F.R.C.P., Andrew J. Rees, F.R.C.P., F.Med.Sci., Hanna Debiec, Ph.D., Jack F.M. Wetzels, M.D., Ph.D., Pierre Ronco, M.D., Ph.D., Peter W. Mathieson, Ph.D., F.R.C.P., and Robert Kleta, M.D., Ph.D.

Background

Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population

Methods

We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method).

Results

In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A2 receptor (PLA2R1) (SNP rs4664308, P=8.6×10?29), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P=8.0×10?93). The association with HLA-DQA1 was significant in all three populations (P=1.8×10?9, P=5.6×10?27, and P=5.2×10?36 in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2).

Conclusions

An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA.

 推荐会议:

第一届国际医学影像和放射学新进展暨学术论著发表策略研讨会
2011 Medical Imaging and Radiological Innovations Conference

会议时间:2011年3月25日--3月27日

会议地点:上海医学院路复旦医学院明道楼

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