Genetics of NIDDM in France: Studies With 19 Candidate Genes in Affected Sib Pairs

• DOI: 10.2337/diab.46.6.1062
• Publication Date: 2013-09-19T17:42:54Z
• Authors: Nathalie Vionnet; El Habib Hani; Suzanne Lesage; Anne Philippi; Jörg Hager; Mathilde Varret; Markus Stoffel; Yukio Tanizawa; Ken C Chiu; Benjamin Glaser; M Alan Permutt; Philippe Passa; Florence Demenais; Philippe Froguel
• Keywords: Candidate gene; Glucokinase

As part of an ongoing search for susceptibility loci NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action linkage with NIDDM. Loci included the G-protein–coupled inwardly rectifying potassium channels expressed β-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R), LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein convertase 2 (PCSK2), cholecystokinin B (CCKBR}, hexokinase 1 (HK1), (HK2), mitochondrial FAD-glycerophosphate dehydrogenase (GPD2), liver muscle forms pyruvate kinase (PKL, PKM), fatty acid–binding (FABP2), hepatic phosphofructokinase (PFKL), serine/threonine phosphatase beta (PPP1CB), lowdensity lipoprotein (LDLR). Additionally, histidine-rich calcium locus (HRC) on chromosome 19q. All regions were microsatellite markers 751 individuals from 172 families at least two patients overt NIDDM (according to World Health Organization criteria) sibship, using nonparametric methods. These comprise 352 possible affected sib pairs 621 defined as having a fasting plasma glucose value >6.1 mmol/1 >7.8 h after oral load. No evidence was found any candidate our population by methods, suggesting that those not major contributors pathogenesis However, some suggestive between more severe form diagnosed before 45 years age, CCKBR (11pl5.4; P = 0.004). Analyses six additional spanning 27 cM l ip confirmed this region. Whether gene lies must be determined further analyses.