Karadoğan Abdullah Hakan, Arikoglu Hilal, Göktürk Fatma, İşçioğlu Funda, İpekçi Süleyman Hilmi
Department of Medical Biology, Faculty of Medicine, Selçuk University, Konya, Turkey.
Department of Statistics, Faculty of Science, Ege University, Izmir, Turkey.
Adv Clin Exp Med. 2018 Jul;27(7):921-927. doi: 10.17219/acem/68985.
The phosphatidylinositol 3-kinase p85 alpha regulatory subunit 1 gene (PIK3R1) encodes the PIK3R1 protein, which plays a direct role in insulin signaling. PIK3R1 (p85 regulatory subunit) connects firmly with the p110 catalytic subunit, and together these proteins form the phosphatidylinositol 3-kinase (PI3K) protein. PI3K is a key protein in the Akt signaling pathway, which regulates cell survival, growth, differentiation, glucose trafficking, and utilization. Defects in the insulin signaling cascade play an important role in the development of insulin resistance, which shares a common genetic basis for metabolic diseases such as type 2 diabetes (T2D), obesity and cardiovascular diseases.
In our study, we investigated the effect of single nucleotide polymorphisms (SNPs) rs3756668 in 3'UTR region, rs706713 and rs3730089 in exons 1 and 6, respectively, rs7713645 and rs7709243 in intron 1, and rs1550805 in intron 6 of PIK3R1 gene on T2D.
This study enrolled a total of 840 individuals, including 427 diabetic individuals (206 obese and 221 non-obese) and 413 nondiabetic individuals (138 obese and 275 non-obese). The target SNPs were analyzed using real-time polymerase chain reaction (RT-PCR). Statistical analysis was performed using SPSS18.0 (IBM Corp., Armonk, USA). The p-values ≤0.05 were considered statistically significant.
The SNPs rs706713 (Tyr73Tyr) and rs3730089 (Met326Ile) located in exons, and rs7713645, rs7709243 and rs1550805 located in introns were determined to be significantly associated with T2D and phenotypic features such as obesity, insulin resistance and the lipid parameters. The association with SNP rs3756668, which is located in the 3'UTR, was not significant.
Our study supports the role of PIK3R1, an important candidate gene due to its critical role in insulin signal transduction, in T2D development.
磷脂酰肌醇3激酶p85α调节亚基1基因（PIK3R1）编码PIK3R1蛋白，该蛋白在胰岛素信号传导中起直接作用。PIK3R1（p85调节亚基）与p110催化亚基紧密相连，这些蛋白共同构成磷脂酰肌醇3激酶（PI3K）蛋白。PI3K是Akt信号通路中的关键蛋白，可调节细胞存活、生长、分化、葡萄糖转运和利用。胰岛素信号级联缺陷在胰岛素抵抗的发生发展中起重要作用，胰岛素抵抗是2型糖尿病（T2D）、肥胖症和心血管疾病等代谢性疾病的共同遗传基础。
在我们的研究中，我们调查了PIK3R1基因3'UTR区域的单核苷酸多态性（SNP）rs3756668、外显子1中的rs706713和外显子6中的rs3730089、内含子1中的rs7713645和rs7709243以及内含子6中的rs1550805对T2D的影响。
本研究共纳入840名个体，包括427名糖尿病个体（206名肥胖个体和221名非肥胖个体）和413名非糖尿病个体（138名肥胖个体和275名非肥胖个体）。使用实时聚合酶链反应（RT-PCR）分析目标SNP。使用SPSS18.0（美国纽约州阿蒙克市IBM公司）进行统计分析。p值≤0.05被认为具有统计学意义。
位于外显子中的SNP rs706713（Tyr73Tyr）和rs3730089（Met326Ile）以及位于内含子中的rs7713645、rs7709243和rs1550805被确定与T2D以及肥胖、胰岛素抵抗和血脂参数等表型特征显著相关。位于3'UTR的SNP rs3756668的相关性不显著。
我们的研究支持PIK3R1作为一个重要候选基因在T2D发生发展中的作用，因其在胰岛素信号转导中起关键作用。
