PBMC中磷酸二酯酶6C的表达水平与2型糖尿病及血糖血脂异常的关系

Relationship between the expression level of phosphodiesterase 6 in PBMC and type 2 diabetes as well as impaired blood glucose and lipid

目的本研究旨在探讨外周血单个核细胞(PBMC)中磷酸二酯酶6(PDE6)相关基因表达水平与2型糖尿病(T2D)和血糖血脂之间的关系。方法通过GEO数据库获取肥胖、胰岛素抵抗(IR)、空腹血糖异常(IFG)和T2D的PBMC芯片中PDE6相关基因的mRNA表达数据,先采用meta分析筛选出潜在的T2D关键基因,再进行其与血糖血脂指标的相关分析以及在肥胖等人群中的差异分析。结果本研究一共纳入8个PBMC芯片数据,共计155个研究对象。meta分析显示,与健康对照组相比,T2D组中的PDE6A、PDE6B、PDE6D、PDE6G和PDE6H的表达差异均无统计学意义(P>0.05),仅PDE6C下调表达呈差异有统计学意义(P<0.05),标准化均数差(SMD)和95%CI为-0.72(-1.24,-0.19),P<0.05。此外,FPG、HbA1c、TC和TG均与PDE6C呈负相关关系(Pearson相关系数依次为-0.835、-0.817、-0.759和-0.755,P<0.05)。差异分析显示,无论机体是否存在IR,与非肥胖者相比,肥胖者PDE6C表达仅呈上调趋势(P>0.05);而肥胖个体在减肥手术治疗后PDE6C的表达显著下调(P<0.05),但BS并不显著下调肥胖T2D个体中PDE6C的表达(P>0.05)。此外,在健康对照组、IFG和T2D组的两两比较中,与健康对照组相比,PDE6C在IFG组仅呈下调表达趋势(P>0.05),但在T2D组则显著下调表达(P=0.011);与IFG组相比,T2D组PDE6C也仅呈下调表达趋势(P>0.05)。结论PBMC中下调表达的PDE6C可能与T2D及血糖血脂水平异常有关。

Objective To investigate the relationship among the gene expression levels related phosphodiesterase 6(PDE6)in peripheral blood mononuclear cells(PBMC)and type 2 diabetes(T2D)as well as blood glucose and lipid.Methods The mRNA expression data sets of PDE6-related genes in PBMC from obesity,insulin resistance(IR),impaired fasting glucose(IFG)and T2D were extracted through GEO database.Next,using the obtained data,we screened out the potential key genes of T2D by meta analysis,and analyzed the correlation among them and blood glucose and lipid indexes as well as the difference of them between subjects with and without obesity(or other cases).Results A total of 8 PBMC data sets were included in this study,with 155 subjects.Meta analysis showed that compared with the healthy control group,the expression of PDE6C was significant downregulated in T2D group[its standardized mean difference(SMD,95%CI)was-0.72(-1.24,-0.19),P<0.05],but not significantly different about PDE6A,PDE6B,PDE6D,PDE6G and PDE6H(P>0.05).Meanwhile,the expression of PDE6C was negatively correlated with the levels of FPG,HbA1c,TC and TG,and the Pearson correlation coefficients were-0.835,-0.817,-0.759 and-0.755,respectively,(P<0.05).Additionally,difference analysis showed that the expression of PDE6C in obese patients was non-significantly upregulated compared with non-obese patients(P>0.05),regardless of whether they had the presence of IR or not.However,compared to before bariatric surgery(BS),the expression of PDE6C in obese individuals was significantly downregulated after the surgery(P<0.05),but not significantly reduced in obese T2D individuals after BS(P>0.05).What′s more,in the one-to-one comparisons among three groups,compared with the healthy control group,the expression of PDE6C was non-significantly down regulated in the IFG group(P>0.05),but significantly reduced in the T2D group(P=0.011);the expression of PDE6C in the T2D group was not significantly decreased in comparison to the IFG group(P>0.05).Conclusion The down-regulated expression of PDE6C in PBMC may be related to T2D and abnormal blood glucose and lipid levels.