11 research outputs found
Association of rs780094 in GCKR with Metabolic Traits and Incident Diabetes and Cardiovascular Disease: The ARIC Study
The minor T-allele of rs780094 in the glucokinase regulator gene (GCKR) associates with a number of metabolic traits including higher triglyceride levels and improved glycemic regulation in study populations of mostly European ancestry. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, we sought to replicate these findings, examine them in a large population-based sample of African American study participants, and to investigate independent associations with other metabolic traits in order to determine if variation in GKCR contributes to their observed clustering. In addition, we examined the association of rs780094 with incident diabetes, coronary heart disease (CHD), and stroke over up mean follow-up times of 8, 15, and 15 years, respectively.Race-stratified analyses were conducted among 10,929 white and 3,960 black participants aged 45-64 at baseline assuming an additive genetic model and using linear and logistic regression and Cox proportional hazards models.Previous findings replicated among white participants in multivariable adjusted models: the T-allele of rs780094 was associated with lower fasting glucose (p = 10(-7)) and insulin levels (p = 10(-6)), lower insulin resistance (HOMA-IR, p = 10(-9)), less prevalent diabetes (p = 10(-6)), and higher CRP (p = 10(-8)), 2-h postprandial glucose (OGTT, p = 10(-6)), and triglyceride levels (p = 10(-31)). Moreover, the T-allele was independently associated with higher HDL cholesterol levels (p = 0.022), metabolic syndrome prevalence (p = 0.043), and lower beta-cell function measured as HOMA-B (p = 0.011). Among black participants, the T-allele was associated only with higher triglyceride levels (p = 0.004) and lower insulin levels (p = 0.002) and HOMA-IR (p = 0.013). Prospectively, the T-allele was associated with reduced incidence of diabetes (p = 10(-4)) among white participants, but not with incidence of CHD or stroke.Our findings indicate rs780094 has independent associations with multiple metabolic traits as well as incident diabetes, but not incident CHD or stroke. The magnitude of association between the SNP and most traits was of lower magnitude among African American compared to white participants
Sports therapy and recreation exercise program in type 2 diabetes: randomized controlled trial, 3-month follow-up
Additional file 2: Figure S2. of ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling
Establishing a 3D lung tissue aggregate co-culture to model drug transporter expression and activity. Relative mRNA expression of ABCB1 and ABCG2 drug transporters in A) 2D monocultures, 3D co-culture aggregates (NS: NHLF-SAEC, HNS: HMVEC-L-NHLF-SAEC), B) in 3D co-culture aggregate (HNS: HMVEC-L-NHLF-SAEC) and normal, healthy lung tissue. mRNA expression is relative to beta-actin. In 2D cultures drug transporter expressions are much lower than in the controls. These expression levels increase in 3D culture conditions and all three cell types are needed to become similar to normal lung tissue expression levels. Data are presented as mean ± SEM, n = 3 C) representative image of ABCG2 protein expression in 3D co-culture aggregate (HNS: HMVEC-L-NHLF-SAEC), scale bar 50 μm, magnification; D) functional activity of ABCB1 and ABCG2 drug transporters in 3D HMVEC-L-NHLF-SAEC co-culture aggregates. Data are presented as mean ± SEM of multidrug resistance activity factor values (MAF), n = 3. MAF values ≥ 20 are considered as active transporter function. (DOCX 655 kb