Genetic Association of the CCR5 Region With Lipid Levels in At-Risk Cardiovascular Patients

Abstract

Background-There is mounting evidence to suggest that chemokine receptor 5 (CCR5) plays an important role in the development and progression of atherosclerosis. A naturally occurring variant of the CCR5 gene CCR532, exists at allele frequencies of typically 10% in European populations and results in a nonfunctional CCR5 receptor. Methods and Results-The CCR5⌬32 deletion and 26 other variants within the chemokine receptor 2-CCR5-chemokine receptor-like protein 2 (CCRL2) gene cluster spanning 59 kilobases of chromosome 3 were genotyped in 5748 subjects from the Treating to New Targets atorvastatin trial to determine whether genetic associations could be identified with circulating lipid values and cardiovascular disease. Our results demonstrate an association between the CCR5⌬32 deletion and increased plasma high-density lipoprotein cholesterol and decreased plasma triglycerides, both of which are beneficial from a cardiovascular perspective. Three single-nucleotide polymorphisms (rs1154428, rs6808835, and rs6791599) in CCRL2 in linkage disequilibrium (r

Ccr5δ32 Polymorphism Not Detected in Hiv Patients in Voluntary Counseling and Testing Moewardi General Hospital Surakarta, Indonesia

“…People homozygous for CCR5Ä32 are naturally resistant to R5 HIV infection and the heterozygous state is associated with up to 2-4 years delay in disease progression (Gupta & Padh, 2012). This polymorphism was found in Caucasians and in Chinese state high (Liu et al, 2012) and exists at allele frequencies of typically 10% in European populations (Hyde et al, 2010). However, to our knowledge, the presence of CCR5Δ32 polymorphisms in Indonesian HIV patients has not been reported.…”

Increased circulating CC chemokine levels in the metabolic syndrome are reduced by low‐dose atorvastatin treatment: evidence from a randomized controlled trial

“…In contrast to eotaxin‐1 and MCP‐1, MIP‐1β levels were not associated with lipid profile or insulin resistance, rather MIP‐1β strongly correlated with CRP and less so with MCP‐1. Accumulating evidence suggests a role for MIP‐1β and its receptor, CCR5, in the pathogenesis of atherosclerosis . Indeed, they may be involved, not only in the recruitment of peripheral monocytes to the developing plaque, but also in adipose tissue dysfunction.…”

“…Among hypertensive subjects, those in the top quartile for serum MIP‐1β were at increased risk of stroke and cardiovascular events over a mean follow‐up period of 37 months . Furthermore, it has been observed that a naturally occurring variant of CCR5 gene, CCR5Δ32 a 32 bp deletion that leads to a non‐functional receptor, is associated with increased plasma HDL and decreased TG in cohorts with established cardiovascular disease …”

CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users

“…We raise this point as the polymorphism in the non-coding region of CCR5 that is shared by HHG*1 and HHG*2 and which distinguishes it from all the other CCR5 haplotypes (named as A29G in Figure 1) is in nearly 100% linkage disequilibrium with a polymorphism in a haplotype of CCRL2 (www.hapmap.org and data not shown) that is ∼31 kb downstream of CCR5 . Recent studies have demonstrated that this CCRL2 haplotype associates with multiple diseases [33], [34].…”