Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD)

<p>Abstract</p> <p>Background</p> <p>Genetic factors as well as environmental factors are important in the development of NAFLD and in this study we investigated associations between polymorphisms of peroxisome proliferators-activated receptor γ coactivator 1α polymorphism (<it>PPARGC1A</it>) and NAFLD.</p> <p>Aims</p> <p>We recruited 115 patients with biopsy-proven NAFLD, 65 with NASH and 50 with simple steatosis, and 441 healthy control subjects and investigated 15 SNPs of <it>PPARGC1A</it>.</p> <p>Results</p> <p>SNP rs2290602 had the lowest <it>p </it>value in the dominant mode (<it>p </it>= 0.00095), and the odds ratio for NAFLD (95% CI) was 2.73 (1.48 – 5.06). rs2290602 was significantly associated with NAFLD even when the most conservative Bonferroni's correction was applied (<it>p </it>= 0.0143). The frequency of the T allele of rs2290602 was significantly higher in the NASH patients than in the control subjects (<it>p </it>= 0.00093, allele frequency mode), and its frequency in the NASH patients tended to be higher than in the simple steatosis patients (<it>p </it>= 0.09). The results of the real-time RT-PCR study showed that intrahepatic mRNA expression of <it>PPARGC1A </it>was lower in the TT group than in the GG or GT group at SNP rs2290602 (p = 0.0454).</p> <p>Conclusion</p> <p>This is the first study to demonstrate a significant association between genetic variations in <it>PPARGC1A </it>and NAFLD. This finding suggested that <it>PPARGC1A </it>polymorphism and lower expression of <it>PPARGC1A </it>mRNA in the liver are an important genetic contribution to etiology of NAFLD.</p

Efficacy of 4′-[methyl-11C] thiothymidine PET/CT before and after neoadjuvant therapy for predicting therapeutic responses in patients with esophageal cancer: a pilot study

Abstract Background 4′-[Methyl-11C] thiothymidine (4DST) has been introduced as a new cell proliferation imaging PET tracer that incorporates into DNA directly. The aim of this prospective study was to evaluate the efficacy of 4DST PET/CT for predicting responses to neoadjuvant therapy in patients with esophageal cancer comparing with FDG PET/CT. Methods Twenty-six patients who had pre- and post-therapeutic 4DST and FDG PET/CT and underwent esophagectomy following neoadjuvant therapy were used for the analysis. Based on pathological findings, patients were divided into two groups: non-responders and responders. The maximum standardized uptake value (SUVmax), metabolic tumor volume, total lesion glycolysis, and total lesion proliferation of the primary lesion were measured for FDG and 4DST PET. Results The pathological diagnosis revealed 16 responders and 10 non-responders. Non-responders showed significantly higher 4DST post-therapeutic SUVmax (postSUVmax) than responders, whereas FDG postSUVmax showed no statistically significant difference (non-responders vs. responders: 4DST, 6.7 vs. 3.3, p = 0.001; FDG, 6.1 vs. 4.5, p = 0.11). Responders showed a greater reduction in percentage changes of 4DST and FDG SUVmax (ΔSUVmax) from baseline to post-therapeutic PET (non-responders vs. responders: 4DST, − 2.9% vs. − 56.7%, p < 0.001; FDG, − 36.3% vs. − 72.6%, p < 0.001). In ROC analysis, ΔSUVmax and postSUVmax with 4DST provided great diagnostic performance for predicting responses (area under the curve: 4DST ΔSUVmax = 0.92, 4DST postSUVmax = 0.88). Conclusions 4DST PET/CT has a great potential for predicting pathologic response to neoadjuvant therapy in patients with esophageal cancer; it may be slightly superior to that with FDG PET/CT