Radanova M, Vasilev V, Dimitrov T, Deliyska B, Ikonomov V, Ivanova D
Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University - Varna, Varna, Bulgaria
Clinics of Nephrology, University Hospital - 'Tzaritza Ioanna - ISUL', Medical University - Sofia, Sofia, Bulgaria.
Lupus. 2015 Mar;24(3):280-9. doi: 10.1177/0961203314555173. Epub 2014 Oct 17.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect substantially any organ in the body. One of its most severe manifestations is lupus nephritis. Hereditary C1q deficiency is strongly related to SLE but there are very few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE. In the present study we evaluated the possible association of gene variants in complement C1q gene cluster with susceptibility to lupus nephritis in a Bulgarian population, focusing on five previously associated with SLE SNPs in other populations.
Thirty-eight patients with lupus nephritis and 185 healthy controls, all from Bulgaria, were genotyped for the five C1q SNPs, rs587585, rs292001, rs172378, rs294179 and rs631090, by quantitive real-time PCR methods. We also determined C1q serum levels of C1q and haemolytic activity of C1q in relation to C1q genotypes.
Lupus nephritis patients and healthy controls had statistically similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, minor G allele in rs172378 was significantly overrepresented in lupus nephritis patients when compared with healthy controls (36% vs. 23%, odds ratio = 1.80, 95% confidence interval = 1.06-3.06, p = 0.029). The SNP rs292001 showed a trend towards lower serum C1q levels in healthy controls. Two SNPs - rs294179 and rs292001 - were in a linkage disequilibrium in patients and healthy controls with different power (healthy controls: r (2 )= 0.6526, D' = 0.842; lupus nephritis patients: r (2 )= 0.491, D' = 0.686). The haplotype C-A-A-T-T in the patient group was associated with lupus nephritis: 7.7% vs. 0.8%, odds ratio = 10.81, 95% confidence interval = 1.45-80.57, p = 0.002.
These results support the implication of the G allele in rs172378 as a risk factor for lupus nephritis in a homozygous status, at least for a Bulgarian population.
系统性红斑狼疮（SLE）是一种全身性自身免疫性疾病，可累及身体的任何器官。其最严重的表现之一是狼疮性肾炎。遗传性C1q缺乏与SLE密切相关，但关于C1q基因簇的单核苷酸多态性（SNP）与SLE发病机制关系的研究很少且不一致。在本研究中，我们评估了补体C1q基因簇中的基因变异与保加利亚人群狼疮性肾炎易感性的可能关联，重点关注先前在其他人群中与SLE相关的5个SNP。
采用定量实时PCR方法，对38例来自保加利亚的狼疮性肾炎患者和185例健康对照进行了5个C1q SNP（rs587585、rs292001、rs172378、rs294179和rs631090）的基因分型。我们还测定了与C1q基因型相关的C1q血清水平和C1q溶血活性。
狼疮性肾炎患者和健康对照在rs587585、rs292001、rs294179和rs631090 SNP的基因型和等位基因频率上在统计学上相似。然而，与健康对照相比，rs172378中的次要G等位基因在狼疮性肾炎患者中显著过量存在（36%对23%，优势比=1.80，95%置信区间=1.06 - 3.06，p = 0.029）。SNP rs292001在健康对照中显示出血清C1q水平较低的趋势。两个SNP - rs294179和rs292001 - 在患者和健康对照中处于不同强度的连锁不平衡状态（健康对照：r² = 0.6526，D' = 0.842；狼疮性肾炎患者：r² = 0.491，D' = 0.686）。患者组中的单倍型C - A - A - T - T与狼疮性肾炎相关：7.7%对0.8%，优势比=10.81，95%置信区间=1.45 - 80.57，p = 0.002。
这些结果支持rs172378中的G等位基因至少在保加利亚人群中作为纯合状态下狼疮性肾炎的危险因素。
