title: Association of C3 and C4A complement types with familial amyloidotic polyneuropathy.
abstract: A mutant variant of the serum protein transthyretin (TTR-met30) appears to be a necessary but not sufficient condition for the development of familial amyloidotic polyneuropathy (FAP). We have studied a number of serum protein markers (alpha 1-antitrypsin, properdin factor B, C3, C4A, C4B, haptoglobin, transferrin and group-specific component) in FAP patients and healthy controls in an attempt to identify additional pathogenic factors which may influence the risk for developing FAP in male and female patients as well as the age of onset of the disease. Statistically significant associations were found in the complement systems C3 and C4A. The C3F variant was significantly increased in all FAP patients with a relative risk (RR) of 2.0, more pronounced in female patients (RR = 2.6) and patients with an early onset of the disease (RR = 4.5). In the FAP patients only the variants A3 and A4 were found in the C4A system. C4A3 was found in all patients, which was significantly higher than in the controls. The remaining serum protein systems showed no statistically significant associations with FAP. The results suggest that genetic variants of complement factors C3 and C4A may interact with the mutant TTR-met30 by modifying the expression and onset of FAP.
authors: Department of Medical Genetics, University of Umeå, Sweden.
authors: P O
authors: PO
authors: Nylander
authors: L
authors: L
authors: Beckman
authors: G
authors: G
authors: Holmgren
authors: L
authors: L
authors: Steen
mesh_terms: D000367:Age Factors; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D003176:Complement C3 / Q000235:genetics*; D015934:Complement C4a / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D013548:Sweden
chemical_list: D015415:Biomarkers; D003176:Complement C3; D015934:Complement C4a