Kidney Week

Abstract: TH-PO810

APOL1: A "Novel" Genetic Variant Associated with Podocytopathy in Chile

Session Information

• Genetic Diseases of the Kidney - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Leiva Gonzalez, Marina, Hospital Intercultural de Nueva Imperial, Temuco, Chile

Marina Leiva Gonzalez,

• Plaza, Anita, Universidad Austral de Chile, Valdivia, Chile

Anita Plaza,

• Tobar, Eduardo, Universidad de Chile, Santiago, Chile

Eduardo Tobar,

• Yáñez, Cristian Emilio, Universidad de Chile, Santiago, Chile

Cristian Emilio Yáñez,

• Romero, Diego, Pontificia Universidad Catolica de Chile., Santiago, Chile

Diego Romero,

• Verdugo, Ricardo A., Universidad de Chile, Santiago, Chile

Ricardo A. Verdugo,

• Mendez, Gonzalo P., Pontificia Universidad Catolica de Chile., Santiago, Chile

Gonzalo P. Mendez,

• Mezzano, Sergio A., Universidad Austral de Chile, Valdivia, Chile

Sergio A. Mezzano,

• Ardiles, Leopoldo G., Universidad Austral de Chile, Valdivia, Chile

Leopoldo G. Ardiles,

• Krall, Paola, Universidad Austral de Chile, Valdivia, Chile

Paola Krall,

Background

The APOL1 G1 risk allele (rs73885319) is associated with kidney disease in African Americans. According to ExAC data, the G1 allele has an uneven distribution, reaching a high frequency (23%) in Africans, but is very rare (0.6%) in the Latino population. In 2016-2017, three patients in Southern Chile affected by kidney disease were identified as homo- or heterozygous G1 carriers. Here, we describe a study as a first effort to determine the prevalence and association of the G1 allele with podocytopathy in Chileans.

Methods

50 FFPE-DNA samples of adult patients with a biopsy-proven podocytopathy and 1666 DNA samples of ChileGenomico DNA repository recruited along the whole country were analyzed to determine prevalence of the APOL1 G1 risk allele. Genetic analysis was performed by PCR combined with (NGS+Sanger) sequencing technology. Genetic association between the G1 allele and podocytopathy was analyzed by a 2x2 contingency table to estimate OR.

Results

Among the 50 cases with a biopsy-proven podocytopathy, 4 subjects carried one risk allele (G1/G0), while 8 out of the 1666 ChileGenomico subjects carried this genotype, resulting a positive genetic association between the allele and the podocytopathy (G1 allele frequency 4% vs. 0.24%; p<0.001). One of the 4 G1/G0 cases was HIV-positive; the second hit remains unknown in the other 3 cases. Odds ratio for the effect of the APOL1 G1 risk allele resulted 19.8 (95% CI 5.7-67.7).

Conclusion

Chilean population has a 1-5% African genetic ancestry that decreases from North to South. To our knowledge, this is the first study in Chile that explores the prevalence of the APOL1 G1 risk allele and its association with a podocytopathy. We confirmed a very low frequency of the APOL1 G1 risk allele dispersed in the Chilean population, but a significant prevalence among patients with podocytopathy. The clinical value of APOL1 risk alleles is still uncertain in our population and second hits in some patients remain unknown. More evidence is needed before considering the APOL1 genotype as an input to define clinical management and ethical issues have to been considered, particularly for the Afrodescendant migrants that have arrived in Chile the last years. Grants FONDECYT 11140242 and 1160465.

Funding

• Government Support - Non-U.S.