C4 polymorphism in multiplex families with insulin dependent diabetes in the Tunisian population: Standard C4 typing methods and RFLP analysis

Jenhani, F.; Bardi, R.; Gorgi, Y.; Ayed, K; Jeddi, M.

doi:10.1016/0896-8411(92)90196-w

Cited by 14 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inherited deficiencies of component 4 (C4) have been implicated in the pathogenesis of type 1 diabetes [113–115], but whether this contributes to susceptibility to infection in type 1 diabetics is not known. By contrast, obesity and elevated insulin levels (as which occurs in type 2 diabetes) appear to be associated with elevations in C3 [116].…”

Section: Diabetes and The Immune Systemmentioning

confidence: 99%

The impact of diabetes on the pathogenesis of sepsis

Koh

Peacock

Poll

et al. 2011

Eur J Clin Microbiol Infect Dis

188

129

View full text Add to dashboard Cite

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones.

show abstract

Section: Diabetes and The Immune Systemmentioning

confidence: 99%

The impact of diabetes on the pathogenesis of sepsis

Koh

Peacock

Poll

et al. 2011

Eur J Clin Microbiol Infect Dis

188

129

View full text Add to dashboard Cite

show abstract

“…The most significant difference was in HERV-K (C4) CN, with most patients having two fewer copies than healthy control subjects. This HERV-K(C4) deficiency is not surprising given previous observations of C4A deficiency in type 1 diabetes and that 95% of C4A genes have the HERV-K(C4) insertion (11)(12)(13)(14)(15). However, HERV-K(C4) is the variant with the greatest difference in median CN and greatest significance (2.3 copies, P = 4.59 3 10 7 ), whereas the difference in C4A is much smaller and less significant (1.1 copies, P = 1.76 3 10 5 ).…”

Section: Type 1 Diabetes Is Associated With Fewer Copies Of Herv-k(c4)mentioning

confidence: 99%

Low HERV-K(C4) Copy Number Is Associated With Type 1 Diabetes

Mason¹,

Speake²,

Gersuk³

et al. 2014

Diabetes

View full text Add to dashboard Cite

Complement component C4 (C4) is a highly variable complement pathway gene situated ∼500 kb from DRB1 and DQB1, the genes most strongly associated with many autoimmune diseases. Variations in C4 copy number (CN), length, and isotype create a highly diverse gene cluster in which insertion of an endogenous retrovirus in the ninth intron of C4, termed HERV-K(C4), is a notable component. We investigated the relationship between C4 variation/CN and type 1 diabetes. We found that individuals with type 1 diabetes have significantly fewer copies of HERV-K(C4) and that this effect is not solely due to linkage with known major histocompatibility complex class II susceptibility alleles. We show that HERV-K(C4) is a novel marker of type 1 diabetes that accounts for the disease association previously attributed to some key HLA-DQB1 alleles, raising the possibility that this retroviral insertion element contributes to functional protection against type 1 diabetes.

show abstract

“…A difference in C4A and C4B gene dosage or an imbalance in production of these proteins has also been associated with several autoimmune diseases [5], including type 1 diabetes [25], myasthenia gravis [26], and others. A real-time polymerase chain reaction (PCR) method for single-step quantification of C4A and C4B gene copies has been developed [27] that has been used to demonstrate a direct relationship between C4 gene dosage and clinical course of hereditary angioedema [28].…”

Section: Introductionmentioning

confidence: 98%