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Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?
Version 1
: Received: 30 April 2024 / Approved: 1 May 2024 / Online: 1 May 2024 (05:05:57 CEST)
How to cite:
ALCÁNTARA-ORTIGOZA, M. A.; Rodríguez-Lozano, A. L.; Estandía-Ortega, B.; González-del Angel, A.; Díaz-García, L.; Rivas-Larrauri, F. E.; Nájera-Velázquez, R. G. Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?. Preprints2024, 2024050040. https://doi.org/10.20944/preprints202405.0040.v1
ALCÁNTARA-ORTIGOZA, M. A.; Rodríguez-Lozano, A. L.; Estandía-Ortega, B.; González-del Angel, A.; Díaz-García, L.; Rivas-Larrauri, F. E.; Nájera-Velázquez, R. G. Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?. Preprints 2024, 2024050040. https://doi.org/10.20944/preprints202405.0040.v1
ALCÁNTARA-ORTIGOZA, M. A.; Rodríguez-Lozano, A. L.; Estandía-Ortega, B.; González-del Angel, A.; Díaz-García, L.; Rivas-Larrauri, F. E.; Nájera-Velázquez, R. G. Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?. Preprints2024, 2024050040. https://doi.org/10.20944/preprints202405.0040.v1
APA Style
ALCÁNTARA-ORTIGOZA, M. A., Rodríguez-Lozano, A. L., Estandía-Ortega, B., González-del Angel, A., Díaz-García, L., Rivas-Larrauri, F. E., & Nájera-Velázquez, R. G. (2024). Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?. Preprints. https://doi.org/10.20944/preprints202405.0040.v1
Chicago/Turabian Style
ALCÁNTARA-ORTIGOZA, M. A., Francisco Eduardo Rivas-Larrauri and Ruth Guadalupe Nájera-Velázquez. 2024 "Does the esv3587290 Copy-Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican versus European Childhood-Onset Systemic Lupus Erythematosus Patients?" Preprints. https://doi.org/10.20944/preprints202405.0040.v1
Abstract
A ~3-kb deletion-type DNA copy-number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor for developing lupus nephritis (LN) in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N=37) or without (N=29) LN, as diagnosed by renal biopsy (N=15), proteinuria (N=33), urinary protein:creatinine ratio >0.2 (N=34), and erythrocyturia and/or granular casts in urinary sediment (N=16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation by Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically-matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium (HWE) by 2 test. Associations between LN and esv3587290 CNV were tested by calculating the Odds Ratio (OR) and using Pearson's 2 tests with a 95% confidence interval and p≤0.05. Contrary to the results described in European-descent populations, the esv3587290 CNV showed a significant protective effect against LN development (OR 0.14, 95% CI 0.066-0.31, p≤0.05), whereas the wild-type homozygous VANGL1 genotype showed a risk trend for LN development (OR 2.15, 95% CI 0.7711-6.18, p≤0.05). Finally, we characterized the precise breakpoint of the esv3587290 CNV as NG_016548.1(NM_138959.3):c.1314+1339_1315-897del (https://databases.lovd.nl/shared/variants/0000918418#00025811) in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.
Keywords
childhood-onset systemic lupus erythematosus; lupus nephritis; VANGL1 gene; DNA copy-number variation; Mexican population
Subject
Medicine and Pharmacology, Pediatrics, Perinatology and Child Health
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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