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Monocyte chemoattractant protein-1 -2518 A/G single nucleotide polymorphism might be associated with renal disease and thrombocytopenia of SLE.

ABSTRACT: There is conflicting evidence on the contribution of the MCP-1 -2518 A>G (rs 1024611) polymorphism to SLE incidence and clinical manifestations. We examined the prevalence of the MCP-1 -2518 A>G polymorphism in SLE patients (n = 199) and controls (n = 250) in Poland. We did not observe a significant difference in the distribution of MCP-1 -2518 A>G polymorphic variants in patients with SLE and healthy individuals. However, we found an association between the GG versus AG and AA genotypes as well as the AG and GG versus AA genotypes with renal manifestations of SLE OR = 3.614 (1.123-11.631, P = 0.0345) and OR = 2.297 (1.301-4.057, P = 0.0046), respectively. We also observed that the MCP-1 AG and GG -genotypes contribute to the occurrence of thrombocytopenia in SLE patients OR = 2.618 (1.280-5.352, P = 0.0089). Our observations indicate that either MCP-1 -2518 G variant can be associated with some clinical findings in patients with SLE.

SUBMITTER: Piotrowski P

PROVIDER: S-EPMC2858281 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Monocyte chemoattractant protein-1 -2518 A/G single nucleotide polymorphism might be associated with renal disease and thrombocytopenia of SLE.

Piotrowski Piotr P Lianeri Margarita M Gasik Robert R Roszak Andrzej A Olesińska Marzena M Jagodziński Paweł P PP

Journal of biomedicine & biotechnology 20100421

There is conflicting evidence on the contribution of the MCP-1 -2518 A>G (rs 1024611) polymorphism to SLE incidence and clinical manifestations. We examined the prevalence of the MCP-1 -2518 A>G polymorphism in SLE patients (n = 199) and controls (n = 250) in Poland. We did not observe a significant difference in the distribution of MCP-1 -2518 A>G polymorphic variants in patients with SLE and healthy individuals. However, we found an association between the GG versus AG and AA genotypes as well ...[more]

PMID: 20414371

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Project description:BackgroundMonocyte chemoattractant protein 1 (MCP-1), acting in concert with its receptor chemokine receptor 2 (CCR2), promotes recruitment of macrophages into atherosclerotic plaque. We examined whether single nucleotide polymorphism (SNP) variants in the MCP-1 or CCR2 genes independently or in combination are associated with carotid artery atherosclerosis in an African American population at increased risk of vascular disease.MethodsFour SNPs in MCP-1 and 1 in CCR2 were genotyped. Carotid artery duplex ultrasonography was used to identify the presence or absence of carotid plaque >1 mm. The study population included 325 apparently healthy 30- to 59-year-old black siblings of 185 probands with premature coronary artery disease (<60 years old). Associations between each independent SNP and the presence of carotid plaque were examined using multivariate logistic regression models adjusted for age, sex, educational level, diabetes, smoking, hypertension, obesity, low-density lipoprotein cholesterol and non-independence within families. Interactions between SNPs in the MCP-1 gene and the SNP in the CCR2 gene were examined by multivariate analysis.ResultsSiblings were 32% males, with a mean age of 46 +/- 7 years, and 77 (24%) demonstrated carotid plaque. In multivariate analyses, the CC genotype of MCP-1 SNP rs2857656 was independently associated with plaque (p = 0.05). Subjects who had both the MCP-1 CC genotype and were heterozygotic or homozygotic for the CCR2 V64I genotype (rs1799864; n = 12) had an even higher risk of carotid atherosclerosis (odds ratio 6.14, 95% confidence interval 1.82-20.73; p = 0.0037).ConclusionThe MCP-1 rs2857656 CC genotype is independently associated with carotid artery plaque in African American from families with premature coronary artery disease. The combination of the MCP-1 CC homozygous genotype and the homozygotic or heterozygote CCR2 V64I genotype is associated with a particularly high prevalence of carotid artery plaque.

Project description:HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages.Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96) or high (n = 96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16 × 10(-5)). While the association was not genome-wide significant (p<1 × 10(-7)), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84 × 10(-6)). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048).These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages as well as in vivo.

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Monocyte chemoattractant protein-1 -2518 A/G single nucleotide polymorphism might be associated with renal disease and thrombocytopenia of SLE.

Publications

Monocyte chemoattractant protein-1 -2518 A/G single nucleotide polymorphism might be associated with renal disease and thrombocytopenia of SLE.

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