Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Diabetes (Impact Factor: 8.47). 05/2008; 57(8):2226-33. DOI: 10.2337/db07-1583
Source: PubMed

ABSTRACT Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear.
We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea.
We confirmed the associations of TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 x 10(-12) < P(unadjusted) < 0.016). In addition, the A allele of rs8050136 at FTO was associated with increased BMI in the control subjects (P(unadjusted) = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations.
Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.

Download full-text


Available from: Hong Kyu Lee, Jun 27, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Worldwide researchers have invested time, effort, and money during the last years to find new genes associated with diabetes susceptibility, such as LOC387761, HHEX, EXT2, and SLC30A8. The aim of the present study was to evaluate whether single-nucleotide polymorphisms (SNPs) of these genes are associated with type 2 diabetes (T2D) and metabolic traits in the Mexican population. We also assessed these SNPs in Mexican indigenous groups to identify a possible inherited susceptibility. Seven SNPs were analyzed in 789 Mexicans (234 control subjects, 455 type 2 diabetic patients, and 100 of indigenous origin), using the KASPar assay (KBioscience Company). Analysis of the data showed an association of the LOC387761 SNP rs7480010 with T2D (p = 0.019). The risk allele A of rs7480010 increased body mass index in diabetic patients (p = 0.01). In addition, there was no association between T2D and the SNPs of HHEX, EXT2, and SLC30A8. Our findings suggest that the SNP rs7480010 (LOC387761) can contribute to a failure in insulin secretion, thus increasing the susceptibility to T2D in Mexicans.
    Genetic Testing and Molecular Biomarkers 01/2011; 15(1-2):79-83. DOI:10.1089/gtmb.2010.0107 · 1.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ,University of Lecce, Italy (piero. lionello@unile. it),University of Bern, Switzerland (bhend@giub. unibe. ch, dmarta@giub. unibe. ch),ISAC-CNR, Italy (A. Buzzi@isac. cnr. it),Tel Aviv University, Israel (shimon@cyclone. tau. ac. il),INM Spain (jansa@inm. es),University of Thessalonoki, Greece (maheras@geo. auth. gr),ARPA, Piemonte, Italy (antonella. sanna@arpa. piemonte. it),Instituto de Meteorologia/Centro de Geofi'sica, Universidade de Lisboa, Portugal (isabel. trigo@meteo. pt),CGUL at University of Lisbon and Universidade Luso'fona Portugal (rmtrigo@fc. ul. pt)
  • [Show abstract] [Hide abstract]
    ABSTRACT: A monolithic regenerative divider by two with a 6-GHz central input frequency has been designed and fully characterized using an improved harmonic balance formulation, suitable to deal with autonomous and phase-locked regimes. The solution paths when the input generator power and frequency are modified have been traced. The output power at the divided frequency has been evaluated as a function of both parameters as well as the output power of the free running oscillator regime. Results have been experimentally verified, and excellent agreement has been obtained. Frequency jumps and hysteresis phenomena often encountered in such devices can be fully analyzed, thus providing a useful tool for a thorough investigation of synchronized devices
    Microwave Symposium Digest, 1992., IEEE MTT-S International; 07/1992