Department of General Practice, Hainan General Hospital, #19, Xiuhua Road, Xiuying District, Haikou, 570311, Hainan, People's Republic of China.
Health Center, Hainan General Hospital, Haikou, 570311, Hainan, People's Republic of China.
BMC Med Genomics. 2021 Oct 30;14(1):257. doi: 10.1186/s12920-021-01105-8.
Type 2 Diabetes (T2D) is the result of a combination of genes and environment. The identified genetic loci can only explain part of T2D risk. Our study is aimed to explore the association between CTNNA3 single nucleotide polymorphisms (SNPs) and T2D risk.
We conducted a 'case-control' study among 1002 Chinese Han participants. Four candidate SNPs of CTNNA3 were selected (rs10822745 C/T, rs7920624 A/T, rs2441727 A/G, rs7914287 A/G), and logistic regression analysis was used to evaluate the association between candidate SNPs and T2D risk. We used single factor analysis of variance to analyze the differences of clinical characteristics among different genotypes. In this study, haplotype analysis was conducted by plink1.07 and Haploview software and linkage disequilibrium (LD) was calculated. The interaction of candidate SNPs in T2D risk was evaluated by multi-factor dimensionality reduction (MDR). Finally, we conducted a false-positive report probability (FPRP) analysis to detect whether the significant findings were just chance or noteworthy observations.
The results showed that CTNNA3-rs7914287 was a risk factor for T2D ('T': OR = 1.33, p = 0.003; 'TT': OR = 2.21, p = 0.001; 'TT' (recessive): OR = 2.09, p = 0.001; Log-additive: OR = 1.34, p = 0.003). The results of subgroup analysis showed that rs7914287 was significantly associated with the increased risk of T2D among participants who were older than 60 years, males, smoking, drinking, or BMI > 24. We also found that rs2441727 was associated with reducing the T2D risk among participants who were older than 60 years, smoking, or drinking. In addition, rs7914287 was associated with T2D patients with no retinal degeneration; rs10822745 and rs7920624 were associated with the course of T2D patients. High density lipoprotein levels had significant differences under different genotypes of rs10822745. Under the different genotypes of rs7914287, the levels of aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase were also significantly different.
We found that CTNNA3 genetic polymorphisms can be used as a new genetic signal of T2D risk in Chinese Han population. Especially, CTNNA3-rs7914287 showed an outstanding and significant association with T2D risk in both overall analysis and subgroup analysis.
2 型糖尿病（T2D）是基因与环境共同作用的结果。已鉴定的遗传位点只能解释部分 T2D 风险。本研究旨在探讨 CTNNA3 单核苷酸多态性（SNP）与 T2D 风险之间的关联。
我们在中国汉族参与者中进行了一项“病例对照”研究。选择 CTNNA3 的四个候选 SNP（rs10822745 C/T、rs7920624 A/T、rs2441727 A/G、rs7914287 A/G），并使用逻辑回归分析评估候选 SNP 与 T2D 风险之间的关联。我们使用单因素方差分析来分析不同基因型之间临床特征的差异。在本研究中，通过 plink1.07 和 Haploview 软件进行单倍型分析，并计算连锁不平衡（LD）。使用多因素降维（MDR）评估候选 SNP 在 T2D 风险中的相互作用。最后，我们进行了虚假阳性报告概率（FPRP）分析，以检测显著发现是否只是偶然或值得注意的观察结果。
结果表明，CTNNA3-rs7914287 是 T2D 的危险因素（“T”：OR=1.33，p=0.003；“TT”：OR=2.21，p=0.001；“TT”（隐性）：OR=2.09，p=0.001；对数加性：OR=1.34，p=0.003）。亚组分析结果表明，rs7914287 与 60 岁以上、男性、吸烟、饮酒或 BMI>24 的参与者 T2D 风险增加显著相关。我们还发现 rs2441727 与 60 岁以上、吸烟或饮酒参与者的 T2D 风险降低有关。此外，rs7914287 与无视网膜变性的 T2D 患者有关；rs10822745 和 rs7920624 与 T2D 患者的病程有关。rs10822745 不同基因型下的高密度脂蛋白水平有显著差异。rs7914287 不同基因型下，天冬氨酸氨基转移酶、丙氨酸氨基转移酶和γ-谷氨酰转移酶水平也有显著差异。
我们发现 CTNNA3 遗传多态性可作为中国汉族人群 T2D 风险的新遗传信号。特别是，CTNNA3-rs7914287 在总体分析和亚组分析中均与 T2D 风险具有显著关联。
