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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.

Author information

1
Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
2
Institute of Genetic Epidemiology, Medical Center and Faculty of Medicine - University of Freiburg, Freiburg, Germany.
3
Division of Nephrology and Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
4
Welch Center for Prevention, Epidemiology, & Clinical Research, The Johns Hopkins University, Baltimore, MD, USA.
5
Department of Epidemiology, The University of Texas Health Science Center at Houston School of Public Health at Houston, Houston, TX, USA.
6
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
7
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
8
Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. pduggal@jhu.edu.

Abstract

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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