Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and a canonical target of antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy and insulin resistance; in the general population, the common P12A variant is associated with a decreased risk of type 2 diabetes (T2D). Whether and how rare variants in PPARG and defects in adipocyte differentiation influence risk of T2D in the general population remains undetermined. By sequencing PPARG in 19,752 T2D cases and controls drawn from multiple studies and ethnic groups, we identified 49 previously unidentified, nonsynonymous PPARG variants (MAF

Year of Publication
2014
Journal
Proc Natl Acad Sci U S A
Volume
111
Issue
36
Pages
13127-32
Date Published
2014 Sep 09
ISSN
1091-6490
URL
DOI
10.1073/pnas.1410428111
PubMed ID
25157153
PubMed Central ID
PMC4246964
Links
Grant list
U01 DK085501 / DK / NIDDK NIH HHS / United States
R00 DK092251 / DK / NIDDK NIH HHS / United States
5U01DK085526 / DK / NIDDK NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
HHSN268201300049C / PHS HHS / United States
U01 DK085524 / DK / NIDDK NIH HHS / United States
U01 DK085545 / DK / NIDDK NIH HHS / United States
HHSN268201300048C / PHS HHS / United States
K08 DK102877 / DK / NIDDK NIH HHS / United States
R01 DK098032 / DK / NIDDK NIH HHS / United States
HHSN268201300047C / PHS HHS / United States
U54HG003067 / HG / NHGRI NIH HHS / United States
HHSN268201300048C / HL / NHLBI NIH HHS / United States
BB/I02593X/1 / Biotechnology and Biological Sciences Research Council / United Kingdom
HHSN268201300049C / HL / NHLBI NIH HHS / United States
R01 GM089652 / GM / NIGMS NIH HHS / United States
HHSN268201300050C / PHS HHS / United States
RC2 DK088389 / DK / NIDDK NIH HHS / United States
HHSN268201300046C / PHS HHS / United States
HHSN268201300047C / HL / NHLBI NIH HHS / United States
U01 DK085526 / DK / NIDDK NIH HHS / United States
HHSN268201300050C / HL / NHLBI NIH HHS / United States
U01 DK085584 / DK / NIDDK NIH HHS / United States
DK085584 / DK / NIDDK NIH HHS / United States
DK085545 / DK / NIDDK NIH HHS / United States
098395 / Wellcome Trust / United Kingdom
R01 HL084553 / HL / NHLBI NIH HHS / United States
DK088389 / DK / NIDDK NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
DK085501 / DK / NIDDK NIH HHS / United States
HHSN268201300046C / HL / NHLBI NIH HHS / United States
GM089652 / GM / NIGMS NIH HHS / United States