In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 7 ( 2021-7-30), p. e0249615-
Abstract:
Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10 -8 ) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10 -8 ) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89–1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO , and rs79967607 is in intron 1 of EPM2A . PLUTO , a lncRNA , regulates transcription of an adjacent gene, PDX1 , that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0249615
DOI:
10.1371/journal.pone.0249615.g001
DOI:
10.1371/journal.pone.0249615.g002
DOI:
10.1371/journal.pone.0249615.t001
DOI:
10.1371/journal.pone.0249615.t002
DOI:
10.1371/journal.pone.0249615.t003
DOI:
10.1371/journal.pone.0249615.t004
DOI:
10.1371/journal.pone.0249615.t005
DOI:
10.1371/journal.pone.0249615.s001
DOI:
10.1371/journal.pone.0249615.s002
DOI:
10.1371/journal.pone.0249615.s003
DOI:
10.1371/journal.pone.0249615.s004
DOI:
10.1371/journal.pone.0249615.s005
DOI:
10.1371/journal.pone.0249615.s006
DOI:
10.1371/journal.pone.0249615.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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