Kidney Week

Abstract: SA-PO593

HLA Alleles Confer Risk to Primary Idiopathic Nephrotic Syndrome in Individuals of Caucasian Ancestry

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Ahram, Dina, Columbia University Medical Center, New York City, New York, United States

Dina Ahram,

• Gillies, C., University of Michigan, Ann Arbor, Michigan, United States

C. Gillies,

• Mitrotti, Adele, Columbia University Medical Center, New York City, New York, United States

Adele Mitrotti,

• Krithivasan, Priya, Columbia University Medical Center, New York City, New York, United States

Priya Krithivasan,

• Bodria, Monica, None, Langhirano, PARMA, Italy

Monica Bodria,

• Pontrelli, Paola, University of Bari-Dept. of Emergency and Organ Transplantation, Bari, Italy

Paola Pontrelli,

• Gesualdo, Loreto, University of Bari, Altamura, BARI, Italy

Loreto Gesualdo,

• Martino, Marida, Pediatric Hospital "Giovanni XXIII" Bari-Italy, Modugno (BA), Italy

Marida Martino,

• Giordano, Mario, Pediatric Hospital Giovanni XXIII, Bari, Italy

Mario Giordano,

• Gigante, Maddalena, University of Foggia, Foggia, Italy

Maddalena Gigante,

• Pisani, Isabella, University of Parma, Bozzolo (Mantova), Italy

Isabella Pisani,

• Amoroso, Antonio, University of Torino , Torino, Italy

Antonio Amoroso,

• D'Agati, Vivette D., Columbia University College of Physicians and Surgeons, New York, New York, United States

Vivette D. D'Agati,

• Appel, Gerald B., Columbia University College of Physicians and Surgeons, New York, New York, United States

Gerald B. Appel,

• Bomback, Andrew S., Columbia University, New York, New York, United States

Andrew S. Bomback,

• Scolari, Francesco, University of Brescia, Montichiari (Brescia), Italy

Francesco Scolari,

• Magistroni, Riccardo, Università di Modena e Reggio Emilia, Modena, Italy

Riccardo Magistroni,

• Caliskan, Y., Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul, Turkey

Y. Caliskan,

• Gharavi, Ali G., Columbia University Medical Center, New York City, New York, United States

Ali G. Gharavi,

• Kiryluk, Krzysztof, Columbia University Medical Center, New York City, New York, United States

Krzysztof Kiryluk,

• Ghiggeri, Gian Marco, G. Gaslini Children Hospital, Genoa, Italy

Gian Marco Ghiggeri,

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt,

• Sampson, Matt G., University of Michigan, Ann Arbor, Michigan, United States

Matt G. Sampson,

• Sanna-Cherchi, Simone, Columbia University Medical Center, New York City, New York, United States

Simone Sanna-Cherchi,

Background

Primary idiopathic nephrotic syndrome (NS) caused by focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) is a frequent cause of end-stage renal disease (ESRD). Despite the identification of several genetic causes, the etiology of NS remains to be fully understood. We investigated the genetic basis of FSGS in a population of Caucasian descent.

Methods

We recruited a heterogeneous population of Caucasian descent (1,153 cases) ascertained for FSGS (88% of the cases) and MCD (12%). A set of independent and meta-analyzed case-control, genome-wide association studies (GWAS) were performed using an additive model with covariate-correction for population stratification in the three Caucasian cohorts (Western European: 301, Italian: 754, Turkish: 98), matched genetically with 2,393 controls. Quality control assessment was carried out according to standard practices.

Results

In a Meta-analysis of three, combined Caucasian cohorts (1153 cases, 2393 controls), a significant association was found for the SNP rs28383303 (OR=1.57, 95%CI: 1.29-1.67, P= 1.48x10^-8) (Figure 1). All three cohorts contributed to the signal without evidence for heterogeneity. The variant was identified in a 50kb haploblock on chromosome 6p21, which contains the gene encoding the HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1).

Conclusion

In line with previously reported findings implicating the HLA system in childhood-onset nephrotic syndrome and membranous nephropathy, our results indicate the association of HLA risk alleles with NS in individuals of Caucasian descent. Our findings allude to a role for HLA in modulating adaptive immunity and suggest a basis for understanding the complex genetic mechanisms of FSGS.

Funding

• Other U.S. Government Support