RESUMO
Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10(-8)), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.
Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Povo Asiático/genética , Estudos de Casos e Controles , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Humanos , Japão , Polimorfismo de Nucleotídeo Único , Proteínas Supressoras da Sinalização de Citocina/genética , Fatores de Transcrição/genéticaRESUMO
OBJECTIVES: The influence of the amount and rate of weight loss on subsequently regaining weight and dropout from treatment in severely obese patients targeting 5% weight loss was investigated. METHODS: A total of 120 consecutive hospital patients with severe obesity (BMI: 42 ± 9 kg/m(2) ) participated in an inpatient program targeting 5% weight loss that involved goal setting, charting weight four times daily, and diet and exercise. They were followed after discharge to assess subsequent regaining of weight and dropout. RESULTS: Mean weight loss was 4.9 ± 2.4% after a mean of 19 days in the hospital, and 43% of the patients achieved the target weight loss (>5%). Over the median 2-year follow-up period, greater than 5% in-hospital weight loss was associated with a significantly lower risk of regaining weight after adjustment for various factors (>5% to ≤7% loss: hazard ratio 0.30 [0.11-0.85] for regaining all of the lost weight and 0.32 [0.13-0.78] for regaining half of the lost weight). No significant relation between the amount or rate of weight loss and dropout from subsequent outpatient treatment was seen. CONCLUSIONS: Successfully achieving the target weight loss in a comprehensive program predicts subsequent maintenance of lower weight without increasing the risk of dropout. Successful in-hospital weight loss might increase the motivation of obese patients.