RESUMO
Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found between IL6 -573G>C and type 2 diabetes. The observed association of the IL6 -174 C-allele with a reduced risk of type 2 diabetes provides further evidence for the hypothesis that immune mediators are causally related to type 2 diabetes; however, because the association is borderline significant, additional data are still needed to confirm this finding.
Assuntos
Diabetes Mellitus Tipo 2/genética , Interleucina-6/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Estudos de Casos e Controles , Genética Populacional , Humanos , Razão de Chances , RiscoRESUMO
Dysregulation of fatty acid metabolism is important in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor (PPAR)alpha is a master regulator of fatty acid catabolism, and PPARalpha activators delay the onset of type 2 diabetes. We examined association between three PPARalpha gene polymorphisms (an A-->C variant in intron 1, the L162V variant, and the intron 7 G-->C variant) and age at diagnosis of type 2 diabetes in 912 Caucasian type 2 diabetic subjects. Individually, PPARalpha gene variants did not influence age at diagnosis, but in combination, the rare alleles of both the intron 1 A-->C (P < 0.001) and intron 7 G-->C (P = 0.025) variants synergistically lowered age at diagnosis (interaction P < 0.001). Overall, the PPARalpha haplotype signficantly influenced age at diagnosis (P = 0.027), with the C-L-C and C-V-C haplotypes (intron 1-L162V-intron 7) accelerating onset of diabetes by 5.9 (P = 0.02) and 10 (P = 0.03) years, respectively, as compared with the common A-L-G haplotype, and was associated with an odds ratio for early-onset diabetes (age at diagnosis
Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , PPAR alfa/genética , Polimorfismo de Nucleotídeo Único/genética , Idade de Início , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Progressão da Doença , Genótipo , Hemoglobinas Glicadas/análise , Humanos , Íntrons , Lipídeos/sangue , Pessoa de Meia-Idade , População Branca/genéticaRESUMO
A survey of all medical specialist registrars in the UK reveals that a large majority oppose shift working patterns because of their adverse impact on training and quality of life, and on continuity and quality of patient care. This conflicts with the current drive to switch virtually all trainees to shifts by 2004, to comply with the European Union Working Time Directive. More debate is urgently needed.