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Human leukocyte antigen association with familial steroid-sensitive nephrotic syndrome

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Abstract

Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood. Cases with the familial occurrence of SSNS suggest that genetics may play a role in the disease. Human leucocyte antigen (HLA) alleles have been associated with SSNS. We present genetic findings in nine families (44 participants), each with at least two affected siblings. A total of 19 patients were affected with familial SSNS. Six of nine families showed linkage to markers on chromosome 6p (27.29–33.97 Mbp) (Hg19), especially to markers D6S1629 and D6S1560 on HLA dense region in this location. Interestingly, we also found linkage of disease phenotype of familial SSNS on chromosome 15 (91.7–96.9 Mbp) (Hg19) with a logarithm of odds (LOD) score Z = 3.02.

Conclusion: Our findings confirm the linkage of HLA markers on chromosome 6, which strengthens the association of HLA alleles in SSNS.

What is Known:

• Human leukocyte antigen (HLA) alleles have been associated with idiopathic steroid-sensitive nephrotic syndrome (SSNS). Only few studies have investigated the association between HLA alleles and familial SSNS.

What is New:

• We present evidence of linkage of familial SSNS to chromosome 6p (27.29–33.97 Mbp) (Hg19), especially to markers D6S1629 and D6S1560 on HLA dense region in this location. We also found linkage of the disease phenotype of familial SSNS on chromosome 15 (91.7–96.9 Mbp) (Hg19) with a logarithm of odds (LOD) score of Z = 3.02 following autosomal recessive inheritance pattern.

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Fig. 1

Abbreviations

AD:

Autosomal dominant

AR:

Autosomal recessive

CNVs:

Copy number variations

EDTA:

Ethylenediaminetetraacetic acid

HLA:

Human leukocyte antigen

INS:

Idiopathic nephrotic syndrome

LOD:

The logarithm of odds

LOH:

Loss of heterozygosity

Mbp:

Megabase pair

OMIM:

Online Mendelian Inheritance in Man

SNP:

Single-nucleotide polymorphism

SRNS:

Steroid-resistant nephrotic syndrome

SSNS:

Steroid-sensitive nephrotic syndrome

UCSC:

University of California, Santa Cruz (genome browser).

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Acknowledgments

We are sincerely grateful for the contribution of the project participants. We thank Mette Nyegaard (Associate Prof., Aarhus University) for insightful correspondence on genotype-phenotype correlations in this study. We also thank Annemette Friis Mikkelsen and Jiri Dusek for their skillful assistance. We apologize to those authors whose work could not be described in this article due to space limitations.

Funding

The project was supported by funds from International Mobility Ph.D. Stipend, Faculty of Health, Aarhus University, Denmark, awarded to Shivani Joshi; Department of Clinical Medicine, Aarhus University, Denmark; and Helen of Ejnar Bjørnows Fond, Denmark.

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Authors and Affiliations

  1. Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus N, Denmark

    Trine Korsgaard, Rene F. Andersen & Søren Rittig

  2. Department of Clinical Medicine, Child and Youth Research Laboratory, Aarhus University, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus N, Denmark

    Shivani Joshi

  3. Department of Pediatrics and Adolescent Medicine, Klinkum Link der Weser, Bremen, Germany

    Kristina Moeller

  4. Department of Pediatrics, Charles University in Prague – 2nd Faculty of Medicine, Praha 5, Czech Republic

    Tomás Seeman

  5. 1st Department of Pediatrics, Children’s Hospital and Medical School Comenius University Bratislava, Bratislava, Slovakia

    Ludmila Podracká

  6. Department of Cellular and Molecular Medicine, Faculty of Health and Medical Science, The Panum Institute, 3B Blegdamsvej, 2200, Copenhagen N, Denmark

    Hans Eiberg

Authors
  1. Trine Korsgaard
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  2. Shivani Joshi
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  3. Rene F. Andersen
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  4. Kristina Moeller
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  5. Tomás Seeman
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  6. Ludmila Podracká
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  7. Hans Eiberg
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  8. Søren Rittig
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Contributions

All authors contributed to the study conception and design. Trine Korsgaard drafted the manuscript and critically revised important essential content. Study conception, design, material preparation, data collection and analysis, and interpretation were performed by Trine Korsgaard, Shivani Joshi, Rene F. Andersen, Kristina Moeller, Tomás Seemann, Ludmila Podracka, Hans Eiberg, and Søren Rittig. All authors have equally contributed in editing the manuscript and approving the final manuscript.

Corresponding author

Correspondence to Trine Korsgaard.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The research protocol was approved by the Central Denmark Region Committees of Biomedical Research Ethics (M-20110080) and the Danish Data Protection Agency (2011-41-6450). Written consent was obtained from adults and parents of minor participants.

Additional information

Communicated by Mario Bianchetti

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Korsgaard, T., Joshi, S., Andersen, R.F. et al. Human leukocyte antigen association with familial steroid-sensitive nephrotic syndrome. Eur J Pediatr 179, 1481–1486 (2020). https://doi.org/10.1007/s00431-020-03634-3

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  • DOI: https://doi.org/10.1007/s00431-020-03634-3

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