FcgRIIIb Gene Copy Number Polymorphism Predisposes To Susceptibility Of IgAN In Chinese

IgAN is the most common form of primary glomerulonephritis and is characterized by depositions of IgA (mainly IgA1) or IgA-containing immune complexes (IgA-ICs) in the glomerular mesangial areas. IgA1 deposits were usually observed with complement 3 (C3) component, and often with IgG, IgM or both in the glomerular mesangial areas. It is one of the important diseases due to ESRD, will disadvantage the healthy of human severe.So far, we still don't know the mechanism of IgA nephropathy, it is considered association with infection, immune reaction, inflammation, heredity and so on. Several studies have identified FcgRIIIb (Fcgr3b) polymorphisms that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the study was to clarify whether Fcgr3b gene copy number polymorphism influence susceptibility to IgAN, or severity in patients with IgAN. Materials and MethodsThe study consisted of 134 healthy Chinese and 131 biopsy-proven IgAN patients in Kidney Disease Centre, First Affiliated Hospital, College of Medicine, Zhejiang University, China, between January, 2004 and July, 2006. 65 patients with grades I -II of pathological damage and 66 patients with grades IV-V of pathological damage. Healthy random blood donors are also from First Affiliated Hospital, College of Medicine, Zhejiang University. The study was approved by the local ethics committee at Zhejiang University, and informed consent was obtained from all subjects. The selection of this group was based on a diagnosis limited to primary glomerulonephritis and with a predominant deposition of IgA in the mesangium. No patients had clinical or histological evidence of systemic diseases, such as systemic lupus erythematosus, Henoch-Schonlein purpura, chronic liver disease, ANCA-related glomerulonephritis or necrotizing vasculitis. Quantitative PCR was carried out using SYBR Green I and analysed by the standard curve method. The variation in Fcgr3b gene copy number was estimated by Southern analysis.Results1. Among group of IgAN, distribution of Fcgr3b gene copy number from zero to four was 1.53%, 48.85%, 39.69%, 6.11%, and 3.82%compared with 0.75%, 35.82 %, 48.51%, 13.43%, and 1.49%, respectively among the group of grade healthy. Difference of gene copy number distribution between the two groups was significant (X~2=8.83, P=0.033). We did not analyse the distribution of zero copy because of the small sample size. P value of one copy vs two copies of Fcgr3b between the two groups was (X~2=3.69, P=0.052). Low copy number (zero and one copy) vs higher copy number (two, three and four copies) of Fcgr3b between the two groups, (X~2=5.14, P =0.024).2. Among the group of grades IV-V, distribution of Fcgr3b gene copy number from zero to four was 1.52%, 56.06%, 36.36%, 4.55%, and 1.52% compared with 1.54%, 41.54%, 43.08%, 7.69%, and 6.15%, respectively among the group of grades I -II. Difference of gene copy number (one copy, two, and three copies) distribution between the two groups was no significant (X~2=2.24, P =0.34). We did not analyses the distribution of zero copy and four copies because of the small sample size. P value of low copy number (zero and one copy) vs higher copy number (two, three, and four copies) of Fcgr3b between the group of grades I - II and the group of grades IV- V was (X~2=2.76, P=0.097).Conclusions1. The Fcgr3b gene copy number distribution between normal and IgAN patients was different.2. Low copy number of Fcgr3b in Chinese is a risk factor for susceptivity of IgA nephropathy.3. There is no association with Fcgr3b gene copy number polymorphism and the severity of IgAN in Chinese patients.