Insights on the relationship between complement component C4 serum concentrations and C4 gene copy numbers in a Western Australian systemic lupus erythematosus cohort
| Autor: | David Groth, R Whidborne, J.D. Wetherall, Christine Bundell, Patricia Martinez, Audrey A. Margery-Muir |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Gene copy Gene Dosage Down-Regulation 03 medical and health sciences 0302 clinical medicine Rheumatology Risk Factors Complement C4b Humans Lupus Erythematosus Systemic Medicine Genetic Predisposition to Disease Copy-number variation Genetic Association Studies Complement (group theory) business.industry Endogenous Retroviruses Complement C4a Western Australia Middle Aged Serum concentration Phenotype 030104 developmental biology Case-Control Studies DNA Viral Cohort Immunology DNA Transposable Elements Female business Biomarkers 030215 immunology |
| Zdroj: | Lupus. 27:1687-1696 |
| ISSN: | 1477-0962 0961-2033 |
| Popis: | The relationship between serum concentration of complement C4 ([C4]) and C4 gene copy number (GCN) was investigated in 56 systemic lupus erythematosus (SLE) patients and 33 age and sex-matched controls in a Western Australian population. C4A and C4B gene copy numbers (C4A & B GCN) together with the presence or absence of the ≈6.4-kb human endogenous retroviral element type K (hereafter HERV-K) in intron 9 were estimated by two TaqMan™ real-time PCR (RT-PCR) assays that measured total C4 and HERV-K GCNs, respectively. There was good correlation between the two methods; however, the HERV-K GCN method showed a positive bias (≈6%) relative to the C4A & B total GCN. Despite individual variation, excellent correlation between total C4 GCN and mean [C4] per GCN was observed for both the SLE and control cohorts ( R2 = 88% and R2 = 99%, respectively). It was noted that serum [C4] was significantly lower in the SLE patients than the controls ( p = 0.006) despite there being no difference between C4A and C4B GCN in both cohorts. The data therefore confirm previous reports that the C4A genes are preferentially associated with the presence of the HERV-K insertion relative to C4B genes and does not support the hypothesis that low [C4] in SLE is explained by low C4A GCNs. There was no evidence also that the presence of the HERV-K insertion in C4 genes influenced [C4]. This study supports the view that low [C4] in SLE patients is due to consumption rather than deficient synthesis related to lower C4A & B GCN. |
| Databáze: | OpenAIRE |
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