RESUMO
Most recently, 1-h hyperglycemia has been recognized as an additional risk factor for type 2 diabetes. To date, previous genome-wide association studies for glycemic traits have a limited impact on the fasting state and 2-h plasma glucose level in an oral glucose challenge. To identify genetic susceptibility in different stages of glucose tolerance, we performed a meta-analysis for glycemic traits including 1-h plasma glucose (1-hPG) from 14 232 non-diabetic individuals in the Korean population. Newly implicated variants (MYL2, C12orf51 and OAS1) were found to be significantly associated with 1-hPG. We also demonstrated associations with gestational diabetes mellitus. Our results could provide additional insight into the genetic variation in the clinical range of glycemia.
Assuntos
2',5'-Oligoadenilato Sintetase/genética , Povo Asiático/genética , Miosinas Cardíacas/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Cadeias Leves de Miosina/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Glicemia/análise , Diabetes Gestacional/genética , Jejum/sangue , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Genótipo , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Gravidez , República da Coreia , Fatores de RiscoRESUMO
To investigate the role of genetic predisposition in the pathogenesis of polycystic ovary syndrome (PCOS) in relation to obesity, we performed a genome-wide association study of PCOS in Koreans (n=1741). PCOS is a heterogeneous endocrinal disorder of uncertain etiology. Obesity is one of the well-known risk factors for PCOS. Genome-wide association study. Women with or without PCOS. A total of 1881 samples were genotyped using Illumina HumanOmni1 Quad v1 and processed by R packages. The PCOS patients were divided into two subgroups according to PCOS diagnostic criteria (Rotterdam and National Institutes of Health (NIH)). For PCOS-associated loci in the two definitions, we successfully confirmed significant associations of GYS2 for body mass index in the discovery stage. We further replicated pleiotropic associations of GYS2 in a childhood obesity study (n=482) and in a gestational diabetes study (n=1710), respectively. Our study provides a preliminary framework upon diverse genetic effects underlying PCOS in Korean women. A newly identified GYS2 gene as a predisposing factor of PCOS might expand understanding of the biological pathways in metabolic and endocrine regulation.
