A missense variant Arg611Cys in LIPE which encodes hormone sensitive lipase decreases lipolysis and increases risk of type 2 diabetes in American Indians.
American Indian
HSL
LIPE
lipolysis
type 2 diabetes
Journal
Diabetes/metabolism research and reviews
ISSN: 1520-7560
Titre abrégé: Diabetes Metab Res Rev
Pays: England
ID NLM: 100883450
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
30
09
2021
accepted:
09
10
2021
pubmed:
17
10
2021
medline:
1
4
2022
entrez:
16
10
2021
Statut:
ppublish
Résumé
Hormone sensitive lipase (HSL), encoded by the LIPE gene, is involved in lipolysis. Based on prior animal and human studies, LIPE was analysed as a candidate gene for the development of type 2 diabetes (T2D) in a community-based sample of American Indians. Whole-exome sequence data from 6782 participants with longitudinal clinical measures were used to identify variation in LIPE. Amongst the 16 missense variants identified, an Arg611Cys variant (rs34052647; Cys-allele frequency = 0.087) significantly associated with T2D (OR [95% CI] = 1.38 [1.17-1.64], p = 0.0002, adjusted for age, sex, birth year, and the first five genetic principal components) and an earlier onset age of T2D (HR = 1.22 [1.09-1.36], p = 0.0005). This variant was further analysed for quantitative traits related to T2D. Amongst non-diabetic American Indians, those with the T2D risk Cys-allele had increased insulin levels during an oral glucose tolerance test (0.07 SD per Cys-allele, p = 0.04) and a mixed meal test (0.08 log The Arg611Cys variant causes a modest impairment in lipolysis, thereby affecting glucose homoeostasis and risk of T2D.
Substances chimiques
Insulin
0
Sterol Esterase
EC 3.1.1.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3504Informations de copyright
© 2021 John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
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