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Sci Rep. 2019 Apr 11;9(1):5941. doi: 10.1038/s41598-019-42202-0.

Rare variants in SLC5A10 are associated with serum 1,5-anhydroglucitol (1,5-AG) in the Atherosclerosis Risk in Communities (ARIC) Study.

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Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Institute of Genetic Epidemiology, Medical Center and Faculty of Medicine - University of Freiburg, Freiburg, Germany.
Division of Nephrology and Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
Welch Center for Prevention, Epidemiology, & Clinical Research, The Johns Hopkins University, Baltimore, MD, USA.
Department of Epidemiology, The University of Texas Health Science Center at Houston School of Public Health at Houston, Houston, TX, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.


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.

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