Clinical Investigation

Kidney International (1990) 38, 332–336; doi:10.1038/ki.1990.205

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis

Richard H Moore, Graham A Hitman, Renato A Sinico, Jukka Mustonen, Julia Medcraft, Ekundayo Y Lucas, Nicholas T Richards, Michael C Venning, John Cunningham, Frank P Marsh and Giuseppe D'Amico

Medical Unit and Department of Nephrology, The London Hospital Medical College, and Renal Unit, St Thomas' Hospital, London, and The Freeman Hospital, Newcastle-upon-Tyne, United Kingdom; San Carlo Hospital, Milan, Italy; and University of Tampere, Tampere, Finland

Correspondence: Dr Richard Moore, Institute of Nephrology, Kidney Research Unit Foundation, Cardiff Royal Infirmary, Newport Road, Cardiff CF2 1SZ, United Kingdom.

Received 27 November 1989; Revised 13 March 1990; Accepted 15 March 1990.

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Abstract

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis. Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN) are immune complex mediated diseases. Moreover, genetic factors may play an important role in their pathogenesis. Recently, restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy chain genes have been described which appear to associate with glomerulonephritis. We have studied RFLPs of the switch region of the IgM (Smu) and IgA1 (Salpha1) heavy chain in MN and IgAN. DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sacl, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to Smu. This probe detects RFLPs at the Smu and Salpha1 loci. The genotypic and allelic frequencies of the Smu, and Salpha1 alleles in IgAN and MN was similar to normal controls. Caucasoid subjects with IgAN from Northern and Southern Europe (Finland and Italy, respectively) were also studied to determine whether an ethnic variation in genetic susceptibility to IgAN exists. The frequency of the Smu and Salpha1 alleles was similar between the patient groups and their respective local healthy controls. These results do not support the recent findings of an association with RFLPs of the Smu, and Salpha1 loci in IgAN and MN, and suggest that the immunoglobulin heavy chain switch region genes are not important in conferring disease susceptibility to IgAN or MN.

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