CCR5 and CCR2 gene polymorphisms in hypertensive patients

Mettimano, Marco; Specchia, Monia; Ianni, A.; Arzani, Dario; Ricciardi, Walter; Savi, L; Romano-Spica, Vincenzo

doi:10.1080/09674845.2003.11783672

Cited by 24 publications

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“…In addition, almost half of the population sample in the study by Zhang et al was Ͼ60 years of age, whereas the mean age of the two previous studies that found an association of CCR5⌬32 with hypertension was considerably younger, at 37.1 and 49.4 years of age. 1,3 This raises the possibility that this polymorphism could increase the risk for early onset of hypertension, although Zhang et al did not find differences in any of the age groups in their study. 6 It is also worth noting that although CCR264I distribution deviated from Hardy-Weinberg equilibrium in the study by Zhang et al, the proportion of homozygotes did not significantly differ between case and control subjects.…”

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confidence: 39%

“…[1][2][3] The involvement of CCR2 is also supported by animal studies with mutant mice that demonstrate that CCR2 influences hypertension-induced inflammation, macrophage recruitment, and vascular remodeling. 4,5 In apparent conflict with previous reports, [1][2][3] in this issue of the Journal Zhang et al found no significant association between CCR5⌬32 and CCR264I polymorphisms in a large case-control study (comprising almost 3000 cases), selected from a commercial DNA repository. 6 Previously the same group reported a 2.8-fold higher prevalence of hypertension in individuals homozygous for the CCR5⌬32 polymorphism than in age-matched control subjects.…”

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confidence: 75%

“…Both CCR5 and CCR2 mutant allele frequencies were also significantly higher in patients with hypertension in an Italian sample (120 case subjects and 340 control subjects) selected from a university hypertension center according to the criteria of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. 3 Moreover, several other reports have suggested a possible role for CCR in cardiovascular pathologic conditions in general.…”

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confidence: 99%

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CCR Polymorphisms and Hypertension

Spica¹,

Mettimano

2006

American Journal of Hypertension

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confidence: 39%

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confidence: 75%

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confidence: 99%

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CCR Polymorphisms and Hypertension

Spica¹,

Mettimano

2006

American Journal of Hypertension

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“…This effect may be more visible in men since it is known that testosterone may promote apoptotic damage of renal cells and also may diminish the expression of chemokine receptors on immunocompetent cells (18,25). Alternatively, the increased risk of diabetic nephropathy associated with functional polymorphisms in CCR5 may be secondary to increased blood pressure in carriers of the risk alleles (26,27). Several authors have shown that carriers of the 32-bp deletion have higher blood pressure than with noncarriers (26,28).…”

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confidence: 99%

“…Alternatively, the increased risk of diabetic nephropathy associated with functional polymorphisms in CCR5 may be secondary to increased blood pressure in carriers of the risk alleles (26,27). Several authors have shown that carriers of the 32-bp deletion have higher blood pressure than with noncarriers (26,28). In the present study, neither HbA 1c nor blood pressure differed between carriers and noncarriers of the risk haplotypes (online appendix [available at http://diabetes.diabetesjournals.org]).…”

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confidence: 99%

Risk of Diabetic Nephropathy in Type 1 Diabetes Is Associated With Functional Polymorphisms in RANTES Receptor Gene (CCR5)

et al. 2005

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Chemokines and their receptors have been implicated in the development of diabetic nephropathy. To determine whether the risk of diabetic nephropathy is influenced by two functional polymorphisms in the regulated upon activation normal T-cell expressed and secreted (RANTES) receptor gene (CCR5), we recruited patients with type 1 diabetes, including 496 case subjects with overt proteinuria or end-stage renal disease and 298 control subjects with normoalbuminuria. Male carriers of the 59029G allele, which is associated with diminished expression of CCR5 on the surface of immunocompetent cells, had significantly higher risk of developing diabetic nephropathy than noncarriers (OR [95% CI] 1.9 [1.2-3.0]). Similarly, male carriers of the 32-bp deletion, which causes truncation of the protein, had significantly higher risk of diabetic nephropathy than noncarriers (2.3 [1.3-4.2]). Combining both polymorphisms, three haplotypes were distinguished: one nonrisk haplotype carrying the 59029A allele and the 32-bp insertion and two risk haplotypes carrying the 59029A allele with the 32-bp deletion and carrying the 59029G allele with the 32-bp insertion. The distribution of these haplotypes differed significantly (P < 0.00001) in men with and without diabetic nephropathy but was not associated with diabetic nephropathy in women. In conclusion, two functional polymorphisms in CCR5 that decrease expression of the RANTES receptor on immunocompetent cells are associated with increased risk of diabetic nephropathy in type 1 diabetes, but only in men. Diabetes 54:3331-3335, 2005 I n diabetic nephropathy, the infiltration of the glomeruli and interstitium by immunocompetent cells is a common finding both in rodent models of diabetes and in biopsy specimens collected from diabetic patients (1,2). Moreover, the increased synthesis of chemokines and other inflammatory mediators by glomerular and tubular cells has been reported in hyperglycemic conditions (2,3). This includes such chemokines as regulated upon activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1␣ and macrophage inflammatory protein-1␤ (4 -5). These molecules are able to recruit to kidney monocytes by binding to chemokine receptors such as CCR1, CCR3, and CCR5 (6).Recent studies have reported that polymorphisms in the RANTES receptor gene (CCR5) were associated with the increased risk of nephropathy in type 2 diabetes in a Japanese population (7) and with a higher risk of kidney rejection among nondiabetic individuals with kidney transplants (8). The present study aims to examine the association of two functional polymorphisms in CCR5 with the risk of diabetic nephropathy in Caucasians with type 1 diabetes.CCR5 has been mapped to the short arm of chromosome 3 within the chemokine receptor gene cluster (9). Recent studies established that this gene comprises three exons spanning a region of about 6 kb. The clinical and functional relevance of many polymorphisms and haplotypes in CCR5 has been reported (10 -13). The most consistent d...

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RNAi Gene Therapy to Combat HIV-1 Infection

Corbeau

2013

Encyclopedia of Molecular Cell Biology and Molecular Medicine

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CCR5 and CCR2 gene polymorphisms in hypertensive patients

Cited by 24 publications

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CCR Polymorphisms and Hypertension

CCR Polymorphisms and Hypertension

Risk of Diabetic Nephropathy in Type 1 Diabetes Is Associated With Functional Polymorphisms in RANTES Receptor Gene (CCR5)

RNAi Gene Therapy to Combat HIV-1 Infection

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