Why the study?
Variants in NPHS2, BMP4, and SDCCAG8 were found to interact with APOL1, but their association with hypertension-attributed CKD and interaction with APOL1 risk variants required determination.
Are polymorphisms in NPHS2, BMP4, and SDCCAG8 associated with an increased risk of hypertension-attributed chronic kidney disease?
Are polymorphisms in NPHS2, BMP4, and SDCCAG8 associated with an increased risk of hypertension-attributed chronic kidney disease?
Polymorphisms in NPHS2 and BMP4 do not independently increase the risk of hypertension-attributed CKD, but may interact with APOL1 risk variants to increase risk.
Background: Genome-wide association studies conducted in African Americans with non-diabetic nephropathy identified single-nucleotide polymorphism (SNP) rs16854341 in podocin ( NPHS2 ) as the most significant SNP to interact with apolipoprotein L1 ( APOL1 ) gene. In replication studies, SNPs in NPHS2 , bone morphogenic protein 4 ( BMP4 ) and serologically defined colon cancer antigen 8 ( SDCCAG8 ) were found to significantly interact with APOL1 . Objective: We determined the association of polymorphisms in NPHS2 , BMP4 and SDCCAG8 gene with hypertension-attributed chronic kidney disease (CKD) and their interaction with APOL1 risk variants. Methods: A total of 181 participants were recruited. After genomic DNA extractions from whole blood, SNPs in NPSH2 (rs16854341), SDCCAG8 (rs2802723) and BMP4 (rs8014363) were genotyped using TaqMan ® SNP assays. Results: We found no association between the risk of kidney disease and rs16854341 (1.25 (95% confidence interval CI [0.59–2.68]); p = 0.558) and rs8013363 (0.96 (95% CI [0.48–1.92]); p = 0.901). There was a trend for an increased risk of kidney disease in those who had two APOL1 risk variants and were major allele homozygotes at rs16854341 (4.78 (95% CI [0.87–26.31]); p = 0.072, adjusted) and at rs8014363 (5.16 (95% CI [0.92–29.87]); p = 0.062, adjusted). Conclusion: We found no associations of the polymorphisms in the NPHS2 , and BMP4 gene with markers of kidney disease in patients with hypertension-attributed CKD. However, in the presence of two APOL1 risk variants, major allele homozygotes had a trend towards an increased risk of kidney disease. Future studies with larger samples are required to further characterize the interactions of these genes with APOL1 .
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Nqebelele et al. (2019) studied this question.
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