%0 Journal Article %J Sci Rep %D 2019 %T Rare variants in SLC5A10 are associated with serum 1,5-anhydroglucitol (1,5-AG) in the Atherosclerosis Risk in Communities (ARIC) Study. %A Loomis, Stephanie J %A Köttgen, Anna %A Li, Man %A Tin, Adrienne %A Coresh, Josef %A Eric Boerwinkle %A Richard A Gibbs %A Donna M Muzny %A Pankow, James %A Selvin, Elizabeth %A Duggal, Priya %K Atherosclerosis %K Deoxyglucose %K Exome Sequencing %K Female %K Humans %K Longitudinal Studies %K Male %K Middle Aged %K Polymorphism, Single Nucleotide %K Risk Factors %K Sodium-Glucose Transport Proteins %X
Serum 1,5-anhydroglucitol (1,5-AG) is an emerging biomarker used to monitor glycemic control in persons with diabetes. We performed whole-exome sequencing, examining the association between rare, coding genetic variants and 1,5-AG among European ancestry (N = 6,589) and African ancestry (N = 2,309) participants without diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) Study. Five variants representing 3 independent signals on chromosome 17 in SLC5A10, a glucose transporter not previously known to transport 1,5-AG, were associated with 1,5-AG levels up to 10.38 µg/mL lower per allele (1,5-AG range 3.4-32.8 µg/mL) in the European ancestry sample and validated in the African ancestry sample. Together these variants explained 6% of the variance in 1,5-AG. Two of these variants (rs61741107, p = 8.85E-56; rs148178887, p = 1.13E-36) were rare, nonsynonymous, and predicted to be damaging or deleterious by multiple algorithms. Gene-based SKAT-O analysis supported these results (SLC5A10 p = 5.13E-64 in European ancestry, validated in African ancestry, p = 0.006). Interestingly, these novel variants are not associated with other biomarkers of hyperglycemia or diabetes (p > 0.2). The large effect sizes and protein-altering, multiple independent signals suggest SLC5A10 may code for an important transporter of 1,5-AG in the kidney, with a potential nonglucose-related effect on 1,5-AG, impacting its clinical utility as a diabetes biomarker in this subpopulation.
%B Sci Rep %V 9 %P 5941 %8 2019 Apr 11 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/30976018?dopt=Abstract %R 10.1038/s41598-019-42202-0