Asghar Aleesha, Firasat Sabika, Afshan Kiran, Naz Shagufta
Department of Zoology, Faculty of Biological Sciences, Quaid-I-Azam University, University Road, Islamabad, 45320, Pakistan.
Department of Zoology, Lahore College for Women University, Lahore, Pakistan.
Mol Biol Rep. 2023 Jan;50(1):57-64. doi: 10.1007/s11033-022-08011-x. Epub 2022 Oct 27.
CDK5 regulatory subunit associated protein 1 like 1 (CDKAL1) encodes a tRNA modifying enzyme involved in the proper protein translation and regulation of insulin production encoded by the CDKL gene. Sequence variations in the CDKAL1 gene lead to the misreading of the Lys codon in proinsulin, resulting in decreased glucose-stimulated proinsulin production. Various polymorphic sequence variants of the CDKAL1 gene such as rs7754840, rs7756992, rs9465871, and rs10946398 are reported to be associated with type 2 diabetes mellitus and gestational diabetes mellitus (GDM) incidence. One of these single nucleotide polymorphisms i.e., rs10946398 has been reported to impact the risk of GDM and its outcomes in pregnant women of different ethnicities i.e., Egypt, Chinese, Korean, Indian, Arab, and Malaysian. Numerous findings have shown that rs10946398 overturns the regulation of CDKAL1 expression, resulting in decreased insulin production and elevated risk of GDM. However, there is no data regarding rs10946398 genotype association with GDM incidence in our population.
In this study, 47 GDM patients and 40 age-matched controls were genotyped for rs10946398 CDKAL1 variant using Tetra primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra ARMS-PCR).
Analysis of the results showed the significant association of the C allele of CDKAL1 SNP rs10946398 (χ = 0.02 p = 0.001) with the risk of GDM development. Conclusively, the results support the role of SNP i.e., rs10946398 of CDKAL1 gene in GDM development in Pakistani female patients. However, future large-scale studies are needed to functionally authenticate the role of variant genotypes in the disease pathogenesis and progression.
细胞周期蛋白依赖性激酶5调节亚基相关蛋白1样蛋白1（CDKAL1）编码一种参与正确蛋白质翻译以及由CDKL基因编码的胰岛素产生调节的tRNA修饰酶。CDKAL1基因中的序列变异会导致胰岛素原中赖氨酸密码子的错读，从而导致葡萄糖刺激的胰岛素原产生减少。据报道，CDKAL1基因的各种多态性序列变体，如rs7754840、rs7756992、rs9465871和rs10946398，与2型糖尿病和妊娠糖尿病（GDM）的发病率相关。据报道，这些单核苷酸多态性之一，即rs10946398，会影响不同种族（即埃及、中国、韩国、印度、阿拉伯和马来西亚）孕妇患GDM的风险及其结局。众多研究结果表明，rs10946398会破坏CDKAL1表达的调节，导致胰岛素产生减少以及GDM风险升高。然而，在我们的人群中，尚无关于rs10946398基因型与GDM发病率关联的数据。
在本研究中，使用四引物扩增不应性突变系统聚合酶链反应（四引物ARMS-PCR）对47例GDM患者和40例年龄匹配的对照进行rs10946398 CDKAL1变体的基因分型。
结果分析显示，CDKAL1单核苷酸多态性rs10946398的C等位基因（χ = 0.02，p = 0.001）与GDM发生风险显著相关。总之，结果支持CDKAL1基因的单核苷酸多态性rs10946398在巴基斯坦女性患者GDM发生中的作用。然而，未来需要大规模研究从功能上验证变异基因型在疾病发病机制和进展中的作用。
