Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

Abstract

Aims/hypothesis Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients.Methods In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. Results Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p=9.4×10 −34 ; 45% vs 18%, p=1.4×10 −16 ), PTPN22 CT/TT (34% vs 26%, p=0.0023; 31% vs 23%, p=0.034), INS VNTR class I/I (69% vs 53%, p=1.3×10 −8 ; 69% vs 51%, p=8.5×10 −5 ) and INS VNTR class IIIA/IIIA (75% vs 63%, p= 4.3×10 −6 ; 73% vs 60%, p=0.008) was increased in young and middle-aged GAD antibodies (GADA)-Diabetologia

Overlap of Genetic Susceptibility to Type 1 Diabetes, Type 2 Diabetes, and Latent Autoimmune Diabetes in Adults

“…Furthermore, it has even been proposed that TCF7L2 genotype status can be used to discriminate between middle-aged antibody-positive patients from those that are young antibody-positive [82].…”

Association of polymorphism rs7903146 gene TCF7L2 with low concentrations of autoantibodies in latent autoimmune diabetes of adults (LADA)

“…В некоторых исследованиях продемонстрировано повы-шение у пациентов с LADA частот аллеля и генотипов полиморфизма rs7903146 гена TCF7L2, ассоциированных с СД2 [10][11][12][13][14]. Но в одном исследовании повышения ча-стот аллелей и генотипов гена TCF7L2, ассоциированных с СД2, у пациентов с LADA обнаружено не было [15].…”

“…Bakhtadze E с соавт. указывают на увеличение частот генотипов СТ/ТТ у лиц с СД в возрасте от 15 до 34 лет с отрицательными антителами к GAD по сравнению с GADA-положительными пациентами (53% против 43%, р=0,0004) [14]. Тем не менее, по результатам одного из исследований ассоциация между полиморфизмом rs7903146 гена TCF7L2 и LADA не была установлена [16].…”

Type 1 and type 2 diabetes—chalk and cheese?

“…With the recent crop of genome-wide association studies taking the tally of loci confidently implicated in the pathogenesis of multifactorial forms of diabetes [3][4][5] to more than 60, it has become possible to use these to explore the 'aetiological architecture' of diabetes. A number of recent papers describe attempts to do just this [6][7][8][9][10][11][12][13][14].…”