甘露糖结合蛋白基因多态性与IgA肾病免疫病理类型的关联

目的根据甘露糖结合蛋白(MBP)基因多态性对其功能的影响，探讨MBP基因多态性与IgA肾病免疫病理间的联系。方法选取1钾例IgA肾病(IgAN)患者，其中77例为肾小球单纯IgA伴沉积，70例为肾小球IgA，IgG，IgM伴C3，C1q沉积。使用PCR-RFLP方法对MBP基因多态性与IgAN免疫沉积的关系进行了观察。结果①本研究中正常人群MBP基因多态性分布与文献报道的华人及高加索人种接近并无显著差异。②IgAN中大量免疫沉积(IgA，IgG，IgM，C3，C1q)患者MBP基因CGC／GAC基因型的发生频率明显高于单纯IgA沉积(IgA，C3)患者(41.4％vs19.5％，P＜0.01)，而CGC／GGC基因型的发生频率明显低于单纯IgA沉积患者(55.7％vs76.6％，P＜0.01)。IgAN的大量免疫沉积患者GAC等位基因的发生频率明显高于单纯IgA沉积患者(0.236vs0.136，P＜0.05)，而GGC等位基因的发生频率明显低于单纯IgA沉积患者(0.764vs0.864，P＜0.05)，GAC等位基因与IgAN的大量免疫沉积明显相关(OR=1.95，95％CI1.06～3.58)

PATTERNS OF GLOMERULAR IMMUNE DEPOSTTION IN IGA NEPHROPATHY BASED ON A GENETIC VARIA-TION:MANNOSE BINDING PROTEIN GENE POLYMORPHISM

Most of the human glomerulonephritis(GN)have immune deposits in the glomenruli and can be characterizedby the pattern of immune deposits. Deposition of mesangial IgA is the main diagnostic feature of IgA nephropathy(IgAN)with in-terindividual difference in the classes of immunoglobulins associated with IgA presentation in various combination. Serum mannosebinding protein(MBP),a host defense molecule,mediates phagocytosis and activates the complements through the lectin pathway.Low level of serrum MBP may result in opsonic deficiency and impaired ability to handle immune complex(IC). The molecular basisof MBP deficiency in human has been found to be due to a single point mutation at codon 54(GGC→GAC)of MBP gene. In thepresent study, we investigated the relationship between the patterns of glomerular immune deposition and MBP gene polymorphismin patients with IgAN. METHODOLOGY The frequencies of the codon 54 mutation in patients with IgAN were investigatedby PCR-RFLP in the present study. IgAN patients were divided into two groups according to the patterns of glomerular immune de-position. Group A( n= 77): patients with glomerular IgA and C3 deposits. Gruop AGM( n = 70) :patients with glomerular IgA, IgG,lgM, C3 and C lq deposits. One hundred and forty normal subjects were used as control. RESULTS The genotype frequency ofGAC heterozygote was significantly higher in Group AGM as compared to Group A(41.4% vs 19.5%, P < 0.01 )or normal sub-jects(41.4% vs 26.4%, P ＜ 0.05) ,while no difference was found in the distribution of MBP genotype between Group A and nor-mal subjects. The allele frequency of GAC mutation was also higher in Group AGM than Group A(0.24 vs 0. 14, P < 0.05) or nor-mal subjects( 0.24 vs 0. 15, P＜ 0.05 ) .XONCLUSION Our findings provide evidence that IgAN patients with abounding im-mune deposits in glomeruli show a higher frequency of codon 54 mutation in MBP gene which is associated with a low serum MBP level. This genetic deficiency may lead to a less effective IC cleating and more accelerated IC deposition in glomeruli during theprocess of disease than those without this mutation. It also indicates that, in the appropriate environmental and genetic context, genepolymorphism may contribute to the interindividual difference in the patterns of glomerular immune deposition in IgAN patients.