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Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus.

ABSTRACT: Heat shock proteins (Hsps) play a role in the delivery and presentation of antigenic peptides and are thought to be involved in the pathogenesis of multifactorial diseases.To investigate genes encoding cytosolic Hsp70 proteins for associations of allelic variants with systemic lupus erythematosus (SLE).Case-control studies of two independent Caucasian SLE cohorts were performed. In a haplotype-tagging single-nucleotide polymorphism approach, common variants of HspA1L, HspA1A and HspA1B were genotyped and principal component analyses were performed for the cohort from the Oklahoma Medical Research Foundation (OMRF). Relative quantification of mRNA was carried out for each Hsp70 gene in healthy controls. Conditional regression analysis was performed to determine if allelic variants in Hsp70 act independently of HLA-DR3.On analysis of common genetic variants of HspA1L, HspA1A and HspA1B, a haplotype significantly associated with SLE in the Erlangen-SLE cohort was identified, which was confirmed in the OMRF cohort. Depending on the cohorts, OR ranging from 1.43 to 1.88 and 2.64 to 3.16 was observed for individuals heterozygous and homozygous for the associated haplotype, respectively. Patients carrying the risk haplotype or the risk allele more often displayed autoantibodies to Ro and La in both cohorts. In healthy controls bearing this haplotype, the amount of HspA1A mRNA was significantly increased, whereas total Hsp70 protein concentration was not altered.Allelic variants of the Hsp70 genes are significantly associated with SLE in Caucasians, independently of HLA-DR3, and correlate with the presence of autoantibodies to Ro and La. Hence, the Hsp70 gene locus appears to be involved in SLE pathogenesis.

SUBMITTER: Furnrohr BG

PROVIDER: S-EPMC3002760 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus.

Fürnrohr Barbara G BG Wach Sven S Kelly Jennifer A JA Haslbeck Martin M Weber Christian K CK Stach Christian M CM Hueber Axel J AJ Graef Daniela D Spriewald Bernd M BM Manger Karin K Herrmann Martin M Kaufman Kenneth M KM Frank Summer G SG Goodmon Ellen E James Judith A JA Schett Georg G Winkler Thomas H TH Harley John B JB Voll Reinhard E RE

Annals of the rheumatic diseases 20100524 11

<h4>Background</h4>Heat shock proteins (Hsps) play a role in the delivery and presentation of antigenic peptides and are thought to be involved in the pathogenesis of multifactorial diseases.<h4>Objective</h4>To investigate genes encoding cytosolic Hsp70 proteins for associations of allelic variants with systemic lupus erythematosus (SLE).<h4>Methods</h4>Case-control studies of two independent Caucasian SLE cohorts were performed. In a haplotype-tagging single-nucleotide polymorphism approach, c ...[more]

PMID: 20498198

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Project description:BackgroundA number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting.MethodWe searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity.ResultsA total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01-5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02-1.44; GG vs. AA: OR 1.45, 95% CI 1.16-1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03-1.29) and its associated haplotype -1082G/-819C/-592C (OR 1.25, 95% CI 1.10-1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02-1.60) and the -1082G/-819C/-592C haplotype (OR 1.24, 95% CI 1.00-1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24-8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19-6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51-0.94) with SLE among Asians.ConclusionThis meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/-819C/-592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.

Dataset Information

Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus.

Publications

Polymorphisms in the Hsp70 gene locus are genetically associated with systemic lupus erythematosus.

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