Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk.
It has recently been suggested that the low-frequency c.136-14_136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14_136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14_136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease.
UMR CNRS 8199, Genomic and Metabolic Disease, Lille, France.
Marcel
M
Marquez
Marlène
M
Huyvaert
John R B
JR
Perry
Richard D
RD
Pearson
Mario
M
Falchi
Andrew P
AP
Morris
Sidonie
S
Vivequin
Stéphane
S
Lobbens
Loïc
L
Yengo
Stefan
S
Gaget
Francois
F
Pattou
Odile
O
Poulain-Godefroy
Guillaume
G
Charpentier
Lena M S
LM
Carlsson
Peter
P
Jacobson
Lars
L
Sjöström
Olivier
O
Lantieri
Barbara
B
Heude
Andrew
A
Walley
Beverley
B
Balkau
Michel
M
Marre
Philippe
P
Froguel
Stéphane
S
Cauchi
D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D025741:HMGA1a Protein / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance; D011972:Receptor, Insulin / Q000235:genetics; D012306:Risk
D025741:HMGA1a Protein; D011972:Receptor, Insulin