Genetic Restriction of AIDS Pathogenesis by an SDF-1 Chemokine Gene Variant

Winkler, Cheryl A.; Modi, William S.; Smith, Michael W.; Nelson, George W.; Wu, Xueyun; Carrington, Mary; Dean, Michael; Honjo, T.; Tashiro, Kai; Yabe, Daisuke; Buchbinder, Susan; Vittinghoff, Eric; Goedert, James J.; O’Brien, Thomas R.; Jacobson, Lisa P.; Detels, Roger; Donfield, Sharyne; Willoughby, Anne; Gomperts, Edward D.; Vlahov, David; Phair, John P.; O’Brien, Stephen J.

doi:10.1126/science.279.5349.389

Cited by 655 publications

(446 citation statements)

References 42 publications

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“…Gene or allele frequency is the occurrence of an allele in a population in relation to all alleles of that gene on the same locus expressed as a fraction. Overall gene frequencies of our analyzed population of CCR2-64I (10.6%; n Ω 206), CCR5D32 (7.6%; n Ω 118), and SDF1-3ƒA (18.9%; n Ω 203) were similar than those seen in populations previously reported (2,3). Forty (19%) and 16 (13.5%) patients were heterozygous, while two patients and one patient were homozygous for CCR2-64I and CCR5D32, respectively.…”

Section: Patient Population and Genotype Distributionsupporting

confidence: 72%

“…To assess the effects of polymorphisms on graft survival, only first hepatic transplants were analyzed. The oligonucleotide primers for SDF1-3ƒA, CCR2-64I and CCR5D32 were used as previously published (2,3,18). PCR products were digested with 5 U MspI at 37 aeC (SDF1-3ƒA wild-type), or BsaBI at 60 aeC (CCR2-64I mutation) (New England Biolabs, MA, USA).…”

Section: Patient Demographicsmentioning

confidence: 99%

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The Impact of Polymorphisms in Chemokine and Chemokine Receptors on Outcomes in Liver Transplantation

Schröppel

Fischereder

Ashkar

et al. 2002

American Journal of Transplantation

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Chemokines and their corresponding receptors likely play a central role in directing mononuclear cells to the graft sites during rejection. Genes for the chemokine stromal derived factor-1 (SDF1) and CC chemokine receptors CCR2 and CCR5 are characterized by polymorphisms which alter their function. We genotyped DNA of 207 liver transplant recipients by PCR or PCR-RFLP for CCR2-64I, CCR5D32, and SDF1-3ƒA polymorphisms, and examined their association on outcomes in liver allograft recipients. Due to the low number of patients homozygous for CCR2-64I and CCR5D32, only the effects of their heterozygous variants were addressed in this study. None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups, or for graft survival. The gene frequency of the SDF1-3ƒA allele was significantly (p Ω0.034) higher in patients who died (29.0%, n Ω 31) compared to recipients still alive (17.1%, n Ω 172). The mean patient survival time post transplant was 134 months in patients with SDF1 wild-type, significantly (log rank p Ω0.014) longer than 98 months in patients with at least one SDF1-3ƒA allele. The CCR2 and CCR5 polymorphisms were not associated with significant differences in mortality rate. In conclusion, CCR2-64I, CCR5D32, and SDF1-3ƒA genotypes did not influence the risk for acute rejection or graft survival. However, in liver allograft recipients SDF1-3ƒA is significantly associated with higher mortality.

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Section: Patient Population and Genotype Distributionsupporting

confidence: 72%

Section: Patient Demographicsmentioning

confidence: 99%

The Impact of Polymorphisms in Chemokine and Chemokine Receptors on Outcomes in Liver Transplantation

Schröppel

Fischereder

Ashkar

et al. 2002

American Journal of Transplantation

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“…Carriers of the A allele in the SDF-1 gene were at increased risk of developing ICA occlusive disease compared with individuals homozygous for the G. The -801A variant of the SDF-1 gene has been associated with genetic restriction of AIDS pathogenesis, as well as with enhanced CD34+ progenitor cell mobilisation from bone marrow [29,30]. Soriano et al have shown an association between high plasma SDF-1 levels and the SDF-1 A allele [31].…”

Section: Discussionmentioning

confidence: 99%

Genetic control of chemokines in severe human internal carotid artery stenosis

et al. 2008

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Background and purpose: Atherosclerosis is an inflammatory disease. Chemokines and chemokine receptors are known to be involved in atherogenesis. Common single nucleotide polymorphisms (SNPs) affect transcription in response to inflammatory stimuli. The aim of this study was to evaluate the correlations between MCP-1, RANTES, SDF-1, CCR2, and CCR5 gene polymorphisms with increased risk of internal carotid artery (ICA) stenosis. Methods: Hundred and twelve patients, consecutively recruited for ICA occlusive disease, and 282 controls were genotyped for MCP-1-2518G, RANTES-403A, CCR5D32, CCR2 V64I, and SDF-1-801A polymorphisms. Results: The frequency of the SDF-1A allele was significantly different between cases and controls: 0.32 vs. 0.20, respectively (OR 1.81; 95% CI 1.25-2.60; p = 0.007). The frequency of the RANTES-403G allele was significantly higher in patients with stenosis >70% (OR, 2.45; 95% CI 1.12-5.71; p = 0.015). No significant differences were observed with the other polymorphisms. Conclusion:The reported results seem to correlate the polymorphisms of the genes encoding for SDF-1, RANTES with pathogenesis and progression of ICA occlusive disease. Although suggestive, these results need confirmation in prospective cross-sectional studies.

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“…Total DNA was extracted from PBMC using a Q1 Amp Blood Kit (QIAGEN, CA) and genotyping was carried out by PCR/RFLP assays as described earlier by Winkler et al [28]. Standard PCR conditions and primers namely for CCR-64I Fwd: 5 0 -CTCGG ATCTTGTGGG-CAACATGATGG-3 0 , Rev: 5 0 -CTGTGAATA A-TTTGCACATTGC-3 0 ; SDF1-3 0 A Fwd: 5 0 -GACCAGTCAACCTGGGCAAA-3 0 , Rev: 5 0 -CACAT-GATGATGGATGAGACAGAGAA-3 0 and; MCP-1-2518-G/A Fwd: 5 0 -TCA CGCCAGCACTGAC-3 0 , Rev: 5 0 -ACTTCAGGAAGGAGTTGT-3 0 were used in a PTC 200 system and PCR amplified products were digested with restriction endonuclease (BsaBI, MspI and PvuII respectively) for 3 h and then separated in 2.0 % agarose-gel electrophoresis [1,28].…”

Section: Genotypingmentioning

confidence: 99%

“…A G to A substitution at position 801 in the 3 0 untranslated region (UTR) of the SDF1 gene (SDF1-3 0 A) has been reported to slow disease progression [28] although in subsequent studies this claim has been refuted [7,14].…”

Section: Introductionmentioning

confidence: 99%

The Distribution of CCR2-64I, SDF1-3′A and MCP1-2518 G/A Genes Polymorphism in a Specific High Risk Group from the Northeastern States West Bengal, and Gorkha Population in India

Roy

Chakrabarti

2012

Indian J. Virol.

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We studied the prevalence and effects of host genetic polymorphisms for the three AIDS restriction genes (ARGs) namely CCR2-64I, SDF1-3 0 A and MCP1-2518 G/A for HIV infection and progression to AIDS using PCR-RFLP analysis on a total of 568 HIV seronegative serum samples collected from a specific high risk and young population hailing from the seven Northeastern states of India (n = 346), West Bengal (n = 96) and Gorkha population (n = 101). In addition, 181 HIV seropositive cases of which 92 inpatient cases in a large tertiary care hospital located at Kolkata were included in the study. HIV prevalence in our study group was 0.52 %. Four cases seroconverted, 25 cases progressed to AIDS and 05 died during the follow up period of 41 months. The genotype percentage of CCR2-64I, SDF1-3 0 A and MCP1-2518 G/A in the Northeastern states were 18.5, 40.3 and 54 % respectively in the seronegative population. Allele frequencies for SDF1-3 0 A in Northeastern states were significantly higher as compared to the Gorkha (21 %) and the North Indian population (24 %). Relative Hazard values were more than 0.9 for progression to AIDS and death. KaplanMeier survival analysis using Cox proportional regression model did not reveal any

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Genetic Restriction of AIDS Pathogenesis by an SDF-1 Chemokine Gene Variant

Cited by 655 publications

References 42 publications

The Impact of Polymorphisms in Chemokine and Chemokine Receptors on Outcomes in Liver Transplantation

The Impact of Polymorphisms in Chemokine and Chemokine Receptors on Outcomes in Liver Transplantation

Genetic control of chemokines in severe human internal carotid artery stenosis

The Distribution of CCR2-64I, SDF1-3′A and MCP1-2518 G/A Genes Polymorphism in a Specific High Risk Group from the Northeastern States West Bengal, and Gorkha Population in India

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