Supplementary Material for: Re-Sequencing of the <b><i>APOL1</i></b>-<b><i>APOL4</i></b> and <b><i>MYH9</i></b> Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression
2015-09-08T00:00:00Z (GMT) by
<b><i>Background:</i></b> In African Americans (AAs), <i>APOL1</i> G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the <i>APOL1</i> loci, since earlier age ESKD is observed in some AAs with one <i>APOL1</i> renal-risk variant, and because the adjacent gene <i>MYH9</i> is associated with nephropathy in populations lacking G1 and G2 variants. <b><i>Methods:</i></b> Re-sequencing was performed across a ∼275 kb region encompassing the <i>APOL1-APOL4</i> and <i>MYH9</i> genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single <i>APOL1</i> G1 or G2 risk variant. <b><i>Results:</i></b> Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare <i>APOL3</i> Gln<sup>58</sup>Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for <i>APOL1</i> G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with <2 <i>APOL1</i> G1 and/or G2 alleles (849 cases; 1,139 controls), the <i>APOL3</i> null variant was nominally associated with ESKD (recessive model, OR 1.81; p = 0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes did not replicate this association. <b><i>Conclusion:</i></b> Additional common variants in the <i>APOL1-APOL4</i>-<i>MYH9</i> region do not contribute significantly to ESKD risk beyond the <i>APOL1</i> G1 and G2 alleles.