Related Experiment Videos
Relation of gene expression (allotypes) of the fourth component of complement to insulin dependent diabetes and its
Insights
Low complement component 4 (C4) levels in insulin-dependent diabetes are linked to gene expression variations. A specific C4B3 variant is more prevalent in diabetics, especially those with microangiopathy, suggesting a genetic link.
Area of Science:
- Immunogenetics
- Diabetology
- Molecular Biology
Background:
- Low concentrations of complement component 4 (C4) are observed in approximately 25% of insulin-dependent diabetes mellitus (IDDM) patients.
- Low C4 levels are associated with diabetic microangiopathy, a common complication of diabetes.
Purpose of the Study:
- To investigate the relationship between C4 gene expression variability and the presence of microangiopathy in IDDM patients.
- To compare C4 gene expression patterns in IDDM patients with and without microangiopathy against healthy controls.
Main Methods:
- Genotyping and analysis of C4A and C4B gene expression in 126 IDDM patients and 93 controls.
- Comparison of C4 gene expression and variant prevalence between diabetic subgroups (with/without microangiopathy) and controls.
Main Results:
- C4A null (non-expression) was found in 13% of IDDM patients versus 0% of controls (p<0.001), correlating with low C4 levels.
- A rare C4B3 variant was significantly increased in IDDM patients (17%) compared to controls (0%) (p<0.001).
- The C4B3 variant prevalence was higher in IDDM patients with microangiopathy (28%) than in those without (9%) (p<0.01).
Conclusions:
- Variations in C4 gene expression contribute to low plasma C4 concentrations in insulin-dependent diabetes.
- The increased prevalence of the C4B3 variant in IDDM patients, particularly those with microangiopathy, suggests a genetic predisposition to diabetic complications.
Abstract:
About a quarter of insulin dependent diabetics have low concentrations of the fourth component of complement (C4), and a low concentration of C4 is associated with diabetic microangiopathy. The variability of the expression of the C4 gene was compared in insulin dependent diabetics with and without microangiopathy and controls. Of the two genes coding for C4, the A gene (C4A) was not expressed--that is, C4A null--in 16 (13%) of the 126 insulin dependent diabetics compared with none of the 93 controls (p less than 0.001), and all these 16 subjects had low concentrations of C4. Lack of expression of the other C4 gene (C4B) was not associated with insulin dependent diabetes, but a rare variant, C4B3, was significantly increased in the diabetics (21/126; 17%) compared with the controls (none) (p less than 0.001). The prevalence of C4B3 was also increased in the diabetics with complications when compared with those without (14/50 (28%) v 7/76 (9%), p less than 0.01). Low plasma C4 concentrations in insulin dependent diabetics are at least partly due to variation in the expression of the C4 gene. The association of the rare C4B3 variant with microangiopathy suggests a genetic component of its aetiology.