UNASSIGNED: Plasma soluble Receptor for Advanced Glycation End-products (sRAGE) is a strong marker of vascular outcomes although evidence on the direction of association is mixed. Compared to whites, blacks have lower levels of sRAGE. We hypothesized that genetic determinants of sRAGE would help clarify the causal role of sRAGE and the black-white difference in sRAGE levels. We conducted a genome-wide analysis of sRAGE in whites and blacks from the @entity731 Risk in Communities Study. Median plasma sRAGE levels were lower in blacks than whites (728 vs. 1067 pg/ml; P<0.0001). The T (vs. C) allele of @entity32983 , a missense variant in @entity4283 , the gene encoding @entity4283 , was associated with approximately 50% lower sRAGE levels in both whites (N = 1,737; P = 7.26x10-16; minor allele frequency (MAF) = 0.04) and blacks (N = 581; P = 0.02; MAF = 0.01). In blacks, the T (vs. C) allele of @entity32984 , intronic to @entity4283 , was associated with 43% lower sRAGE levels (P = 2.22x10-8; MAF = 0.10) and was nearly absent in whites. These @entity4283 SNPs explained 21.5% and 26% of the variation in sRAGE in blacks and whites, respectively, but did not explain the black-white difference in sRAGE. These SNPs were not significantly associated with @entity204 , @entity301 , @entity6 , @entity712 , or @entity740 in whites (N = 8,130-9,017) or blacks (N = 2,293-2,871) (median follow up ~20 years). We identified strong genetic determinants of sRAGE that did not explain the large black-white difference in sRAGE levels or clearly influence risk of clinical outcomes, suggesting that sRAGE may not be a causal factor in development of these outcomes.

Genetics of Plasma Soluble Receptor for Advanced Glycation End-Products and Cardiovascular Outcomes in a Community-based Population: Results from the XXXX Risk in Communities Study.

@entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity32984 :: ('rs2071288', 'SNP') :: ['rs2071288'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity301 :: ('MESH:D003327', 'Disease') :: ['coronary heart disease'] @entity740 :: ('MESH:D051436', 'Disease') :: ['chronic kidney disease'] @entity32983 :: ('rs2070600', 'SNP') :: ['rs2070600'] @entity731 :: ('MESH:D050197', 'Disease') :: ['Atherosclerosis'] @entity4283 :: ('177', 'Gene') :: ['AGER', 'RAGE'] @entity204 :: ('MESH:D003643', 'Disease') :: ['incident death']
@entity731 :: (MESH:D050197,Disease) :: ['Atherosclerosis']
