Low-Frequency Variants in HMGA1 Are Not Associated With Type 2 Diabetes Risk

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 2; pp. 524 - 530
• Main Authors: MARQUEZ, Marcel, HUYVAERT, Marlene, PATTOU, Francois, POULAIN-GODEFROY, Odile, CHARPENTIER, Guillaume, CARLSSON, Lena M. S, JACOBSON, Peter, SJÖSTRÖM, Lars, LANTIERI, Olivier, HEUDE, Barbara, WALLEY, Andrew, BALKAU, Beverley, PERRY, John R. B, MARRE, Michel, FROGUEL, Philippe, CAUCHI, Stephane, PEARSON, Richard D, FALCHI, Mario, MORRIS, Andrew P, VIVEQUIN, Sidonie, LOBBENS, Stephane, YENGO, Loic, GAGET, Stefan
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2012
• Subjects: Biological and medical sciences; Diabetes; Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology and Diabetes; Endocrinopathies; Endokrinologi och diabetes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genes; Genetic aspects; Genetics/Genomes/Proteomics/Metabolomics; Genome-Wide Association Study; Genomes; Genotype; HMGA1a Protein - genetics; Humans; Insulin Resistance; Medical sciences; Receptor, Insulin - genetics; Risk; Risk factors; Type 2 diabetes; White people; France; Endocrinopathy; Type 2 diabetes; Variant; Metabolic diseases; Low frequency; Risk factor
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db11-0728

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.