Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

Alcántara-Ortigoza, Miguel Angel; Rodríguez-Lozano, Ana Luisa; Estandía-Ortega, Bernardette; González-del Angel, Ariadna; Díaz-García, Luisa; Rivas-Larrauri, Francisco Eduardo; Nájera-Velázquez, Ruth Guadalupe

doi:10.3390/children11060712

Open AccessBrief Report

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

by

Miguel Angel Alcántara-Ortigoza

^1,*

,

Ana Luisa Rodríguez-Lozano

²

,

Bernardette Estandía-Ortega

¹

,

Ariadna González-del Angel

¹

,

Luisa Díaz-García

³

,

Francisco Eduardo Rivas-Larrauri

²

and

Ruth Guadalupe Nájera-Velázquez

²

¹

Laboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico

²

Servicio de Inmunología, Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico

³

Departamento de Metodología de la Investigación, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico

^*

Author to whom correspondence should be addressed.

Children 2024, 11(6), 712; https://doi.org/10.3390/children11060712

Submission received: 30 April 2024 / Revised: 4 June 2024 / Accepted: 5 June 2024 / Published: 10 June 2024

(This article belongs to the Special Issue Diagnosis, Treatment and Care of Pediatric Rheumatology)

Download

Browse Figure

Versions Notes

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 in lupus nephritis (LN) development 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 = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), 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 using 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 using the χ² test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson’s χ² tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034–0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119–0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del 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

Share and Cite

MDPI and ACS 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. Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients? Children 2024, 11, 712. https://doi.org/10.3390/children11060712

AMA Style

Alcántara-Ortigoza MA, Rodríguez-Lozano AL, Estandía-Ortega B, González-del Angel A, Díaz-García L, Rivas-Larrauri FE, Nájera-Velázquez RG. Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients? Children. 2024; 11(6):712. https://doi.org/10.3390/children11060712

Chicago/Turabian Style

Alcántara-Ortigoza, Miguel Angel, Ana Luisa Rodríguez-Lozano, Bernardette Estandía-Ortega, Ariadna González-del Angel, Luisa Díaz-García, 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 Childhood-Onset Systemic Lupus Erythematosus Patients?" Children 11, no. 6: 712. https://doi.org/10.3390/children11060712

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 Childhood-Onset Systemic Lupus Erythematosus Patients? Children, 11(6), 712. https://doi.org/10.3390/children11060712

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI