The two closely linked genes are located on chromosome 6p, between HLA-B and -DR. Several reports have established complete C4B deficiency as the major genetic risk factor for IgA nephropathy (RR = 6.5; p = 0.0004).
Their findings include the following: (1) partial deficiencies for C2, beta 1H (H), properdin (P), or C4 binding protein (C4BP) in four patients with end-stage renal disease, (2) an association between the C3*F allele with IgA nephropathy in the combined group of unrelated patients from Kentucky and the Mid-South, (3) the occurrence of C4B deficiency in two siblings with IgA nephropathy, and (4) an association between C4A deficiency and poor outcome in patients with IgA nephropathy diagnosed as adults.
Their findings include the following: (1) partial deficiencies for C2, beta 1H (H), properdin (P), or C4 binding protein (C4BP) in four patients with end-stage renal disease, (2) an association between the C3*F allele with IgA nephropathy in the combined group of unrelated patients from Kentucky and the Mid-South, (3) the occurrence of C4B deficiency in two siblings with IgA nephropathy, and (4) an association between C4A deficiency and poor outcome in patients with IgA nephropathy diagnosed as adults.
Their findings include the following: (1) partial deficiencies for C2, beta 1H (H), properdin (P), or C4 binding protein (C4BP) in four patients with end-stage renal disease, (2) an association between the C3*F allele with IgA nephropathy in the combined group of unrelated patients from Kentucky and the Mid-South, (3) the occurrence of C4B deficiency in two siblings with IgA nephropathy, and (4) an association between C4A deficiency and poor outcome in patients with IgA nephropathy diagnosed as adults.
These findings indicate that abnormally regulated PCNA expression in PBMC may play an important role in the progression of IgA nephropathy, and that PCNA expression in PBMC may be a useful indicator of disease activity.
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.
These results suggest that HLA-DP region genes are not important in conferring disease susceptibility to IgAN and do not influence clinical disease expression.
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.
TGF-beta 1 mRNA was detected in 68% (24 of 35) of patients with active, and 70% (7 of 10) inactive IgA nephropathy, but in only 18% (3 of 17) normal (P < 0.005), and 27% (4 of 15) disease controls.
Using RT-PCR methods, IL-6 mRNA was detected in the glomeruli of renal biopsy specimens obtained from patients with IgA nephropathy and lupus nephritis.
IL-6 transcripts were identified in 37% (13 of 35) of patients with active IgA nephropathy, compared with 6% (1 of 17) normal controls (P = 0.015), with no significant increase in IgA remission, or disease control groups.
The gene transcription of 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in renal tissue of patients with IgA nephropathy and mesangial proliferative glomerulonephritis were analyzed by amplification of reverse transcribed mRNA with polymerase chain reaction (PCR).
To determine the frequency of complement 4 (C4) deficiency among the patients with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN), C4 and factor B protein allotypes and the DNA restriction fragment length polymorphism (RFLP) of C4, steroid 21-hydroxylase (21OHase), HLA DQ beta and DR beta chain genes were studied.
We studied a large North American Caucasian population of patients with biopsy proven IgA nephropathy for polymorphisms of HLA-A,B,C, HLA-DR, HLA-DQ and HLA-DP using a combination of serologic phenotyping and polymerase chain reaction sequence specific oligonucleotide probe (PCR-SSOP) hybridization genotyping.