背景:CDK5调节亚基相关蛋白1(CDKAL1)编码一种tRNA修饰酶,该酶参与由CDKL基因编码的正确蛋白质翻译和胰岛素产生的调节。CDKAL1基因的序列变异导致胰岛素原中Lys密码子的误读,导致葡萄糖刺激的胰岛素原生产减少。据报道,CDKAL1基因的各种多态性序列变体,例如rs7754840,rs7756992,rs9465871和rs10946398与2型糖尿病和妊娠糖尿病(GDM)的发病率有关。这些单核苷酸多态性之一,即,据报道,rs10946398会影响不同种族孕妇的GDM风险及其结局,即埃及,中文,韩语,印度人,Arab,和马来西亚。许多发现表明rs10946398推翻了CDKAL1表达的调节,导致胰岛素产生减少和GDM风险升高。然而,在我们人群中,没有rs10946398基因型与GDM发病率相关的数据.
方法:在本研究中,使用四引物扩增难治性突变系统聚合酶链反应(TetraARMS-PCR)对47名GDM患者和40名年龄匹配的对照进行rs10946398CDKAL1变体的基因分型。
结果:结果分析表明CDKAL1SNPrs10946398的C等位基因与GDM发展风险显着相关(χ2=0.02p=0.001)。最后,结果支持SNP的作用,即CDKAL1基因rs10946398在巴基斯坦女性GDM发展中的作用。然而,未来需要进行大规模的研究来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.
BACKGROUND: 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.
METHODS: 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).
RESULTS: Analysis of the results showed the significant association of the C allele of CDKAL1 SNP rs10946398 (χ2 = 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.