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J Medcraft

Publications and source records attributed to J Medcraft.

5 recordsLinked to original sources
PubMed1996

HLA-DQ gene polymorphism in primary IgA nephropathy in three European populations.

MHC Class II genes may contribute to susceptibility to IgA nephropathy (IgAN). We have previously identified a restriction fragment length polymorphism (RFLP) of the DQB1 region that associated with IgAN in British Caucasoids. However, another group, while demonstrating a DQB1 association, was unable to confirm our finding. MHC molecules are heterodimers consisting of an alpha and beta chain, and thus polymorphism of the DQA1 alpha chain may also be important to disease pathogenesis in IgAN. Therefore, we have determined DQA1 alleles and re-examined DQB1 alleles in British Caucasoids with IgAN using an approach that can differentiate between the common DQ alleles; we have also extended our studies to Caucasoid populations from Northern and Southern Europe, thereby addressing the possibility of variation in genetic susceptibility between populations. DNA was prepared from IgAN patients (British, N = 105; Italian, N = 71; Finnish, N = 48) and healthy controls (British, N = 111; Italian, N = 63; Finnish, N = 41). DQA1 alleles were identified by TaqI RFLP and Southern blotting; alleles that could not be fully resolved by Taq Southern blotting were identified by PCR-RFLP. DQB1 alleles were identified by polymerase chain reaction (PCR) based technique (PCR-RFLP). No consistent association of DQ alleles were found between the populations studied. In British patients a decreased frequency of DQB1*0201 was observed (P = 0.008), in Finnish patients a decreased frequency of DQB1*0602 was observed (P = 0.01), and in Italian patients no association between DQ markers and IgAn was found. These data demonstrate population variation in disease association, but no strong or consistent association in the DQ region.

Alleles↗
PubMed1993

Autoimmune renal disease and tumour necrosis factor beta gene polymorphism.

The genes encoding tumour necrosis factors (TNF) are located within the major histocompatibility complex. Since TNF may be involved in the pathogenesis of autoimmune disease the purpose of the present study was to investigate TNF beta gene polymorphism in two types of immune complex mediated glomerulonephritis, IgA nephropathy (IgAN) and idiopathic membranous glomerulonephritis (IMN) and to compare them with IDDM and healthy controls. DNA was studied by Southern-blot hybridisation methods using Nco I digestion and a TNF beta probe; two alleles were detected size 5.5 kb and 10.5 kb. In healthy controls (n = 107), 9% were 5.5 homozygotes, 47% heterozygotes and 44% 10.5 homozygotes. The corresponding figures in IMN (n = 51) were 21.5%, 61% and 17.5% (p = 0.002), in IDDM (n = 42) 24%, 50% and 26% (p = 0.027) and in IgAN (n = 77) 2.5%, 65% and 32.5% (p = 0.025). The increase in 5.5 homozygotes in both IMN and IDDM was found to be due to an increased frequency of the haplotype A1-B8-TNF beta 5.5-DR3 seen in both these diseases; whereas in IgAN the increased frequency of the 10.5 kb allele can be explained by an association of a Taq 1DQB1-T2 allele with the TNF beta 10.5 allele. These results demonstrate an association of TNF beta gene polymorphism with IMN and IgAN and confirm the associations found in IDDM. Although these disease associations can be explained by linkage disequilibrium with extended MHC haplotypes, a direct role of genetically determined TNF production in the etiology of these diseases remains to be excluded.

Alleles↗
PubMed1992

HLA-DP region gene polymorphism in primary IgA nephropathy: no association.

Many features suggest that a genetically mediated abnormality of the IgA immune response is central in the pathogenesis of IgA nephropathy (IgAN). Candidate disease susceptibility genes include those encoding the MHC class II antigens, HLA-DR, -DQ, and -DP, and we have recently described an HLA-DQB1 association in IgAN. Polymorphisms of the HLA-DP region loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and dermatitis herpetiformis (DH). We have therefore examined restriction fragment length polymorphisms (RFLPs) of the DP alpha and DP beta chain genes (DPA1 and DPB1 respectively) in IgAN, and have studied three caucasoid populations (North, Mid, Southern Europe) to determine whether ethnic variation in genetic susceptibility exists. DNA was extracted from blood (IgAN, UK n = 89, Italy n = 75, Finland n = 49; Controls, UK n = 99, Italy n = 54, Finland n = 45), and studied by Southern blot hybridization techniques using the restriction enzymes BgI II and Msp I and cDNA 32P-labelled DPA1 and DPB1 probes respectively. The frequency distribution of the DPA1 and DPB1 fragments was similar between the three caucasoid IgAN patient groups compared to their respective controls. There was no association of DPA1 or DPB1 RFLPs with clinical features. These results suggest that HLA-DP region genes are not important in conferring disease susceptibility to IgAN and do not influence clinical disease expression. Moreover, different immunogenetic mechanisms operate in IgAN, CD, and DH.

Glomerulonephritis, IGA↗
PubMed1990

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 (S mu) and IgA1 (S alpha 1) 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 Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and allelic frequencies of the S mu and S alpha 1 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 S mu and S alpha 1 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 S mu and S alpha 1 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.

Blotting, Southern↗