Brief Report: Identification of MTMR3 as a Novel Susceptibility Gene for Lupus Nephritis in Northern Han Chinese by Shared‐Gene Analysis With IgA Nephropathy. Issue 10 (October 2014)

• Record Type: Journal Article
• Authors: Zhou, Xu‐jie; Nath, Swapan K.; Qi, Yuan‐yuan; Cheng, Fa‐juan; Yang, Hai‐zhen; Zhang, Yan; Yang, Wanling; Ma, Jian‐yang; Zhao, Ming‐hui; Shen, Nan; Zhang, Hong
• Is Part Of: Arthritis & rheumatology. Volume 66:Issue 10(2014)
• Page Start: 2842
• Page End: 2848
• Publication Date: 2014-10
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38749
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38749-sec-0001" sec-type="section"> <title>Objective</title> <p>Several novel susceptibility genes for systemic lupus erythematosus (SLE) and IgA nephropathy have been identified in recent genome‐wide association studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases of the kidney, they may share common disease mechanisms that overlap with genetic susceptibility. To test this hypothesis, we sought to identify genetic variants associated with IgA nephropathy in lupus nephritis.</p> </sec> <sec id="art38749-sec-0002" sec-type="section"> <title>Methods</title> <p>In the first stage, 500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500 healthy controls were enrolled. Fifteen single‐nucleotide polymorphisms (SNPs) that had the topmost association signals with IgA nephropathy were selected for further testing in patients with lupus nephritis. Three independent cohorts from Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed the functional significance of identified noncoding variants on regulatory motifs and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.</p> </sec> <sec id="art38749-sec-0003" sec-type="section"> <title>Results</title> <p>In addition to associations with <italic>HLA</italic> gene polymorphisms, genetic variants of <italic>MTMR3</italic> in 22q12 showed associations with lupus nephritis (for rs9983A, OR 1.61 [95% CI 1.19–2.19], <italic>P</italic> = 2.07 × 10<sup>−3</sup>) compared to healthy controls in the first stage. Associations were replicated and reinforced among northern Han Chinese (for lupus nephritis patients versus SLE patients without nephritis, <italic>P</italic> = 0.01) but not southern Han Chinese, although significant genetic heterogeneity was observed. Conservative and regulatory features of rs9983 were predicted in in silico analyses. In expression analysis, we observed lower <italic>MTMR3</italic> transcription levels in samples of blood with rs9983A and in renal biopsy samples from lupus nephritis and IgA nephropathy patients.</p> </sec> <sec id="art38749-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our results suggest that the <italic>MTMR3</italic> gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in SLE. However, widespread replication of these experiments, fine mapping, and functional assays are required to establish this connection.</p> </sec> </abstract>