CC chemokine receptor 5 polymorphism in chronic periaortitis

Area of Science:

• Genetics and Immunology
• Vascular Biology
• Rare Diseases

Background:

• Chronic periaortitis (CP) is a rare fibro-inflammatory condition affecting the abdominal aorta, encompassing idiopathic retroperitoneal fibrosis (IRF) and inflammatory abdominal aortic aneurysm (IAAA).
• The role of genetic factors, specifically chemokine receptor polymorphisms, in CP pathogenesis remains under investigation.

Purpose of the Study:

• To investigate the association between the CC chemokine receptor 5 (CCR5)Δ32 polymorphism and susceptibility to chronic periaortitis (CP).
• To determine if this polymorphism differentially affects the risk of developing IRF versus IAAA.
• To explore the influence of established atherosclerotic disease on this association.

Main Methods:

• Genotyping of the CCR5Δ32 polymorphism in 100 CP patients and 180 healthy controls.
• Subgrouping CP patients into IRF and IAAA categories.
• Analysis of patients with and without established atherosclerotic diseases (ischaemic heart disease, cerebrovascular disease, peripheral arterial disease).

Main Results:

• The CCR5Δ32 genotype distribution differed between CP patients and controls (P=0.01).
• The CCR5Δ32 allele was more frequent in CP patients (OR 2.8) and significantly more so in IAAA patients (OR 10.0, P=0.0001) compared to controls.
• The CCR5Δ32 allele was notably more prevalent in IAAA patients without atherosclerotic disease (OR 34.0, P=0.00001) and more frequent in IAAA than IRF patients (OR 6.4, P=0.001).

Conclusions:

• The CCR5Δ32 polymorphism is associated with an increased risk of developing the aneurysmal form of CP (IAAA).
• This genetic association is particularly pronounced in IAAA patients without other established atherosclerotic conditions.
• These findings suggest a potential role for chemokines in the pathophysiology of CP, especially IAAA.