Genetic Basis of Health Disparity in Childhood Nephrotic Syndrome

Abstract

Nephrotic syndrome is the most common glomerular disease in children. There is wide variation in the incidence of nephrotic syndrome in different populations, with a higher incidence in children of South Asian descent. However, nephrotic syndrome with a more indolent course and poor prognosis is more common in African American children. The disparity in the prevalence and severity of nephrotic syndrome is likely due to complex interactions between environmental and biological factors. Recent advances in genome science are providing insight into some of the biological factors that may explain these disparities. For example, risk alleles in the gene encoding apolipoprotein L1 (APOL1) have been established as the most important factor in the high incidence of chronic glomerular diseases in African Americans. Conversely, the locus for childhood steroid-sensitive nephrotic syndrome in the gene encoding major histocompatibility complex-class II-DQ-alpha 1 (HLA-DQA1) is unlikely to be the explanation for the high incidence of steroid-sensitive nephrotic syndrome in Asian children because the same variants are equally common in whites and African Americans. There is a need for collaborative large-scale studies to identify additional risk loci to explain disparities in disease incidence and response to therapy. Findings from such studies have the potential to lead to the identification of new therapeutic targets for nephrotic syndrome.

Keywords: APOL1; African American; HLA-DQA1; Nephrotic syndrome; alleles; apolipoprotein L1 (APOL1); biological factors; childhood; genetics; health disparities; pediatric; race/ethnicity; review.