title: Evaluation of variant A45T in NEUROD1/BETA2 for its association with type 2 diabetes mellitus.
abstract: Heterozygous loss-of-function mutations in NEUROD1 have been identified as a very rare cause of maturity-onset diabetes of the young and neonatal diabetes. Previous studies showed that a common A45T variant located in NEUROD1 was inconsistently associated with type 2 diabetes mellitus (T2DM) in different ethnic populations. This study aimed to evaluate the contribution of variant A45T in the genetic pathogenesis of T2DM. A case-control study in a Chinese Han population was conducted, which included 3,554 (1,155 males/2,399 females) patients with T2DM and 4,181 (1,798 males/2,383 females) control subjects from 13 different regions of China. The A45T variant was genotyped by the Illumina GoldenGate platform. A meta-analysis was used to estimate the effects of variant A45T in populations from different ethnic backgrounds. No association in Chinese Han subjects was confirmed in our case control study. A relationship between variant A45T and postprandial glucose was observed in the control group (β = 0.05, p = 0.002). Meta-analyses did not find an association of this polymorphism with T2DM in Chinese, Japanese, and East Asian descent, but did for European descent Caucasians (odds ratio = 1.15, 95 %CI 1.03-1.28, p = 0.01). Our study suggests the variant A45T does not play a major role in the development of T2DM in East Asian descent, and the role in European descent Caucasian needs to be confirmed.
authors.affiliation: Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Center, Beijing, 100044, China.
authors.forename: Xueyao
authors.initials: X
authors.lastname: Han
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xiao
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.forename: Wenying
authors.initials: W
authors.lastname: Yang
authors.forename: Linong
authors.initials: L
authors.lastname: Ji
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D044465:White People / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C093970:NEUROD1 protein, human