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Objective To investigate the effect of resveratrol on miRNA-106b in Alzheimer′s disease ( AD ) animal model.Methods Fifty Kunming male mice were divided into five groups by completely randomized block sampling.The five groups included three dosage resveratrol groups , an AD model group and a control group.The AD models were established in one month prior to treatments. Subsequently, from the 31st day various doses of resveratrol were provided intragastricly for 60 days.Then the memory function was observed by the step-down test.Meanwhile, the varying expressions of APP , P62, ApoA1, miRNA-106b, ABCA1 were tested in each group to determine whether there is the binding site for miRNA-106b in APP 3′UTR sequence.Results Compared with the control group by step-down test, the memory function of the AD model group mice decreased in different degree , which in the drug treatment group was higher than that in the model group (P<0.05).Compared with the AD group, the expression of APP (1.131 ±0.035) in the drug treatment group was higher than that in the model group (0.652 ± 0.026), while the P62 (0.412 ±0.022) and ApoA1 (0.534 ±0.032) were lower than the model group ( all P<0.05 ).High and medium dose groups of resveratrol treatment reduced varying degrees of APP (0.733 ±0.018,0.929 ±0.019,F=177.733) levels, and increased P62(0.954 ±0.035,0.633 ±0.015, F=434.5 ) and ApoA1 ( 1.042 ±0.051, 0.824 ±0.034, F=286.582 ) levels ( all P<0.05 ).The expression of miRNA-106b (0.464 ±0.313) and ABCA1(0.293 ±0.042) in the model group was lower than that in the control group (miRNA-106b 1.064 ±0.032, F=238.159; ABCA1 0.781 ±0.027,F=341.61;both P<0.05).The miRNA-106b (0.843 ±0.034, 0.601 ±0.012) and ABCA1 (0.882 ± 0.025, 0.624 ±0.036) levels in the high, medium dose resveratrol treatment groups increased to different extent ( both P<0.05 ).After the drug treatment , luciferase reporter vector experiments showed that the APP 3′UTR sequence contains the binding site of miRNA-106b.Conclusions APP is one of the target genes of miRNA-106b.Resveratrol is capable of improving AD by enhancing the expression of miRNA-106b and down-regulating the target genes including APP , P62 and ApoA1.This provides a new theoretical basis for the clinical treatment of AD.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the association between the two single nucleotide polymorphisms located in catechol-O-methyltransferase (COMT) gene and type 2 diabetes mellitus (T2DM)in Han population in Guangdong province.</p><p><b>METHODS</b>Two tagSNPs (rs4646312 and rs4680) were picked out from COMT gene. Using the SNPscan(TM) Kit, SNP genotyping was then performed, in two cohorts, including 595 cases and 725 controls. Finally, Chi-square test, logistic regression model and other methods were employed for statistical analysis.</p><p><b>RESULTS</b>The frequencies of TT, CT and CC of rs4646312 appeared to be 304(51.1%), 234(39.3%)and 57 (8.6%) in cases, 323 (44.6%), 319 (44.0%) and 83(11.4%)in controls, respectively. The frequencies of GG,GA and AA of rs4680 were 311(52.4%), 236 (39.8%) and 46(7.8%)in cases, 417(57.7%), 265 (36.6%) and 41 (5.7%) in controls, respectively.</p><p><b>RESULTS</b>showed that SNP rs4646312 was significantly associated with T2DM both in allelic association analysis (P = 0.020,OR = 1.26, 95%CI:1.04-1.53)and in recessive model (P = 0.022, OR = 1.35, 95% CI:1.05-1.74)after adjustment for sex,BMI and TG. The association between rs4680 and T2DM was not significant, but BMI was remarkably different among the three genotypes of rs4680 after controlling for other factors.</p><p><b>CONCLUSION</b>SNP rs4646312 of COMT gene was associated with the increased risk of T2DM in Han population in Guangdong province. However, rs4680 was not significantly associated with T2DM.</p>