PI3K/ATK/GSK3β信号通路相关miRNA多态性与中国人群2型糖尿病的关联
Association of MiRNA Polymorphisms Involved in the PI3K/ATK/GSK3β Pathway with T2DM in a Chinese Population.
作者信息
Zhou Xing, Yang Man, Yang Ying, Xu Fan, Wang Feiying, Jiao Ming, Tao Wenyu, Li Yiping
机构信息
Department of Endocrinology, The Affiliated Hospital of Yunnan University & The Second People's Hospital of Yunnan Province, Kunming, Yunnan, People's Republic of China.
Kunming Medical University, Kunming, Yunnan, People's Republic of China.
出版信息
Pharmgenomics Pers Med. 2025 Feb 14;18:71-84. doi: 10.2147/PGPM.S487873. eCollection 2025.
BACKGROUND
Single nucleotide polymorphisms (SNPs) in miRNA genes can influence the expression of miRNAs that modulate the PI3K/AKT/GSK3β pathway and play crucial roles in type 2 diabetes mellitus (T2DM) susceptibility. The purpose of this study was to investigate the association of SNPs in miRNA genes targeting the PI3K/AKT/GSK3β pathway with T2DM.
METHODS
This case-control study included 1,416 subjects with T2DM and 1,694 non-diabetics. Eleven SNPs in miRNA genes (rs895819 in miR-27a, rs11888095 in miR-128a, rs2292832 in miR-149, rs6502892 in miR-22, rs13283671 in miR-31, rs1076063 and rs1076064 in miR-378a, rs10061133 in miR-449b, rs3746444 in miR-499a and rs678956 and rs476364 in miR-326) involved in PI3K/AKT/GSK3β pathway were genotyped by TaqMan Genotyping Assay, and the associations of these SNPs with T2DM were analyzed using online SHesis and SNPstats.
RESULTS
The results showed that miR-378a rs1076064 G allele could be a protective factor against T2DM (p<0.001, OR=0.828; 95% CI:0.749-0.916), whereas the miR-31 rs13283671 C allele could increase the risk of developing T2DM (p=0.003, OR=1.193; 95% CI:1.060-1.342). In addition, the miR-378a rs1076063A-rs1076064G haplotype could be a protective against T2DM (p<0.001, OR=0.731; 95% CI:0.649-0.824). According to inheritance mode analysis, compared with the AA-AG genotype, the GG genotype of rs1076064 showed a protective effect in T2DM in the recessive mode (p<0.01, OR=0.71; 95% CI: 0.59-0.84). For rs13283671, compared with the TT genotype, the CT-CC genotype showed a risk effect in T2DM in the dominant inheritance model (p<0.01, OR=1.29; 95% CI: 1.12-1.49). Genotype-Tissue Expression (GTEx) Portal database analysis showed that miR-31 rs13283671 CT and CC genotypes had lower AKT expression than TT genotypes.
CONCLUSION
In conclusion, rs13283671 in miR-31 and rs1076064 in miR-378a involved in the PI3K/AKT/GSK3β pathway were associated with T2DM susceptibility in a Chinese population.
背景
微小RNA（miRNA）基因中的单核苷酸多态性（SNP）可影响miRNA的表达，这些miRNA可调节PI3K/AKT/GSK3β信号通路，并在2型糖尿病（T2DM）易感性中起关键作用。本研究旨在探讨靶向PI3K/AKT/GSK3β信号通路的miRNA基因中的SNP与T2DM的相关性。
方法
本病例对照研究纳入了1416例T2DM患者和1694例非糖尿病患者。采用TaqMan基因分型技术对参与PI3K/AKT/GSK3β信号通路的11个miRNA基因中的SNP（miR-27a中的rs895819、miR-128a中的rs11888095、miR-149中的rs2292832、miR-22中的rs6502892、miR-31中的rs13283671、miR-378a中的rs1076063和rs1076064、miR-449b中的rs10061133、miR-;499a中的rs3746444以及miR-326中的rs678956和rs476364）进行基因分型，并使用在线SHesis和SNPstats分析这些SNP与T2DM的相关性。
结果
结果显示，miR-378a rs1076064的G等位基因可能是T2DM的保护因素（p<0.001，OR=0.828；95%CI：0.749-0.916），而miR-31 rs13283671的C等位基因可能增加患T2DM的风险（p=0.003，OR=1.193；95%CI：1.060-1.342）。此外，miR-378a rs1076063A-rs1076064G单倍型可能对T2DM具有保护作用（p<0.001，OR=0.731；95%CI：0.649-0.824）。根据遗传模式分析，与AA-AG基因型相比，rs1076064的GG基因型在隐性模式下对T2DM具有保护作用（p<0.01，OR=0.71；95%CI：0.59-0.84）。对于rs13283671，与TT基因型相比，CT-CC基因型在显性遗传模型中对T2DM具有风险作用（p<0.01，OR=1.29；95%CI：1.12-1.49）。基因型-组织表达（GTEx）门户数据库分析显示，miR-31 rs13283671的CT和CC基因型的AKT表达低于TT基因型。
结论
总之，参与PI3K/AKT/GSK3β信号通路的miR-31中的rs13283671和miR-378a中的rs1076064与中国人群的T2DM易感性相关。
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