Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of type 2 diabetes mellitus and dyslipidemia, but not coronary artery disease in a Chinese Han population.

Background: Relationships of the polymorphisms in fat mass and obesity-associated gene (FTO) and peroxisome proliferator-activated receptor delta gene (PPARD) with metabolic-related diseases remain to be clarified. Methods: One thousand three hundred and eighty-one subjects were enrolled. Metabolic-related diseases including obesity, dyslipidemia, hyperhomocysteinemia, hyperuricemia, hypertension, type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) were defined based on diagnostic criteria. FTO rs9939609 and rs17817449, and PPARD rs2016520 and rs2267668 polymorphisms were genotyped by using polymerase chain reaction-restricted fragment length polymorphism method. Results: Patients with T2DM or dyslipidemia had a higher frequency of AA, AT or AA + AT genotypes as well as A allele of FTO rs9939609 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.04 for all). Patients with T2DM or dyslipidemia had a higher frequency of GG, GT or GG + GT genotypes as well as G allele of FTO rs17817449 polymorphism than those free of T2DM or dyslipidemia (P ≤ 0.03 for all). Multivariate logistic regression analyses showed that FTO rs9939609 and rs17817449 polymorphisms were independently associated with T2DM as well as dyslipidemia after adjustment for age, sex, smoking and other metabolic diseases. FTO rs9939609 and rs17817449 polymorphisms were not associated with obesity, hyperhomocysteinemia, hyperuricemia, hypertension and CAD. Obese or T2DM carriers of the AA or AT genotype of the FTO rs9939609 polymorphism had a higher prevalence of dyslipidemia compared to non-obese or non-T2DM carriers of the AA or AT genotype (P = 0.03 for both). Among the carriers of GG or GT genotype of the FTO rs17817449 polymorphism, the prevalence of dyslipidemia in obese patients was higher than that in non-obese subjects (P < 0.01). PPARD rs2016520 and rs2267668 polymorphisms were not correlated with any of the metabolic-related diseases in the study population. Conclusion: Minor alleles of FTO rs9939609 and rs17817449 polymorphisms confer a higher risk of T2DM and dyslipidemia, and the risk is further increased among obese individuals. PPARD rs2016520 and rs2267668 polymorphisms are not associated with metabolic-related diseases.

Total Glucosides of Paeony Attenuates Ulcerative Colitis via Inhibiting TLR4/NF-κB Signaling Pathway.

The therapeutic effects and mechanisms of action of total glucosides of paeony (TGP) in treating ulcerative colitis remain to be clarified. Mouse model of ulcerative colitis was treated with TGP and the indexes including scores of disease activity index, gross morphologic damage and histological damage, and inflammatory and oxidative stress markers were determined. Patients with ulcerative colitis received TGP capsule therapy and the indexes including efficacy of colonoscopy and histology, scores of Ulcerative Colitis Activity Index (UCAI) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and inflammatory parameters were assessed. The expressions of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were measured in colonic tissues of mice and patients. TGP treatment significantly increased weight, decreased scores of disease activity index, gross morphologic damage and histological damage, and reduced the levels of tumor necrosis factor-α, interleukin-1ß, malondialdehyde and myeloperoxidase in mouse model. Patients treated with TGP capsule had significantly higher relief rates of diarrhea, abdominal pain, and bloody purulent stool, decreased UCAI and increased SIBDQ scores, and lower levels of erythrocyte sedimentation rate, C-reactive protein and CD4+/CD8+ T-cell ratio than those patients with routine therapy. The overall response rate of TGP capsule was significantly higher than that of routine therapy. TGP treatment significantly suppressed the expressions of TLR4 and NF-κB in colonic tissues of both mouse model and patients with UC. TGP shows a good therapeutic effect on ulcerative colitis in animals and human patients, and the underlying mechanisms may be related to the inhibition of TLR4/NF-κB signaling by TGP.