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Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Research Article

Phosphatidylinositol 3-kinase Glu545Lys and His1047Tyr Mutations are not Associated with T2D

Author(s): Imadeldin Elfaki*, Rashid Mir, Faisel M. Abu-Duhier, Roaid Khan and Mohammed Sakran

Volume 16, Issue 8, 2020

Page: [881 - 888] Pages: 8

DOI: 10.2174/1573399815666191015142201

Price: $65

Abstract

Background: Insulin resistance initiated in peripheral tissues induces type 2 diabetes (T2D). It occurs when insulin signaling is impaired.

Introduction: Phosphatidylinositol 3-kinases (PI3K) are important for insulin signaling. Single nucleotide polymorphisms of the PI3K gene have been associated with T2D.

Methods: We have investigated the association of Glu545Lys and His1047Tyr mutations of phosphatidylinositol- 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene with T2D. We have screened 103 T2D patients and 132 controls for Glu545Lys mutation, and 101 T2D patients and 103 controls for the His1047Tyr mutation from a Saudi cohort using AS-PCR.

Results: Our results indicated that there is no association between the GA genotype of rs104886003 (Glu545Lys) and T2D, OR= 0.15 (95% CI: 0.007-3.28), RR= 0.29(0.02-3.72), P value= 0.23. The A allele is also not associated with T2D diabetes, OR= 1.01(95% CI: 0.70-1.46), RR=1.00(0.85-1.18), P value=0.91. Results showed that CT genotype of rs121913281 (His1047Tyr) was not associated with T2D, OR=0.94(95% CI: 0.23-3.9), RR= 0.97(0.48-1.97), P-value = 0.94, and T allele was also not associated with T2D, OR=1.06 (95% CI: 0.71-1.56), RR= 1.02(0.84-1.24), P-value =0.76.

Conclusion: We conclude that the A allele of rs104886003 may not be associated with T2D. The T allele of rs121913281 may also not associated with T2D. However, future studies with larger sample sizes and in different populations are recommended.

Keywords: Phosphatidylinositol 3-kinase, type 2 diabetes, Glu545Lys (rs104886003), His1047Tyr (rs121913281), single nucleotide polymorphism, insulin resistance, mutations.

[1]
Sacks DB, Arnold M, Bakris GL, et al. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care 2011; 34(6): e61-99.
[http://dx.doi.org/10.2337/dc11-9998] [PMID: 21617108]
[2]
Al-Nozha MM, Al-Maatouq MA, Al-Mazrou YY, et al. Diabetes mellitus in Saudi Arabia. Saudi Med J 2004; 25(11): 1603-10.
[PMID: 15573186]
[3]
Alhowaish AK. Economic costs of diabetes in Saudi Arabia. J Family Community Med 2013; 20(1): 1-7.
[http://dx.doi.org/10.4103/2230-8229.108174] [PMID: 23723724]
[4]
Cantley J, Ashcroft FMQ. Q & A: insulin secretion and type 2 diabetes: why do β-cells fail? BMC Biol 2015; 13: 33.
[http://dx.doi.org/10.1186/s12915-015-0140-6] [PMID: 25982967]
[5]
Franks PW. The complex interplay of genetic and lifestyle risk factors in type 2 diabetes: an overview. Scientifica (Cairo) 2012.2012482186
[http://dx.doi.org/10.6064/2012/482186] [PMID: 24278702]
[6]
Finelli C, Sommella L, Gioia S, La Sala N, Tarantino G. Should visceral fat be reduced to increase longevity? Ageing Res Rev 2013; 12(4): 996-1004.
[http://dx.doi.org/10.1016/j.arr.2013.05.007] [PMID: 23764746]
[7]
Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne) 2013; 4: 37.
[http://dx.doi.org/10.3389/fendo.2013.00037] [PMID: 23542897]
[8]
Ye J. Mechanisms of insulin resistance in obesity. Front Med 2013; 7(1): 14-24.
[http://dx.doi.org/10.1007/s11684-013-0262-6] [PMID: 23471659]
[9]
Manna P, Jain SK. Phosphatidylinositol-3,4,5-triphosphate and cellular signaling: implications for obesity and diabetes. Cell Physiol Biochem 2015; 35(4): 1253-75.
[http://dx.doi.org/10.1159/000373949] [PMID: 25721445]
[10]
Di Zazzo E, Feola A, Zuchegna C, et al. The p85 regulatory subunit of PI3K mediates cAMP-PKA and insulin biological effects on MCF-7 cell growth and motility. ScientificWorldJournal 2014.2014565839
[http://dx.doi.org/10.1155/2014/565839] [PMID: 25114970]
[11]
Chen P, Deng YL, Bergqvist S, et al. Engineering of an isolated p110alpha subunit of PI3Kalpha permits crystallization and provides a platform for structure-based drug design. Protein science: a publication of the Protein Society 2014.23(10): 1332-40..
[http://dx.doi.org/10.1002/pro.2517]
[12]
Burke JE, Vadas O, Berndt A, Finegan T, Perisic O, Williams RL. Dynamics of the phosphoinositide 3-kinase p110δ interaction with p85α and membranes reveals aspects of regulation distinct from p110α. Structure 2011; 19(8): 1127-37.
[http://dx.doi.org/10.1016/j.str.2011.06.003] [PMID: 21827948]
[13]
Riehle RD, Cornea S, Degterev A. Role of phosphatidylinositol 3,4,5-trisphosphate in cell signaling. Adv Exp Med Biol 2013; 991: 105-39.
[http://dx.doi.org/10.1007/978-94-007-6331-9_7] [PMID: 23775693]
[14]
Elfaki I, Mir R, Almutairi FM, Duhier FMA. Cytochrome p450: polymorphisms and roles in cancer, diabetes and atherosclerosis. Asian Pac J Cancer Prev 2018; 19(8): 2057-70.
[http://dx.doi.org/10.22034/APJCP.2018.19.8.2057] [PMID: 30139042]
[15]
Jha CK, Mir R, Elfaki I, et al. Potential impact of MicroRNA-423 gene variability in coronary artery disease. Endocr Metab Immune Disord Drug Targets 2019; 19(1): 67-74.
[http://dx.doi.org/10.2174/1871530318666181005095724] [PMID: 30289085]
[16]
Mir R, Jha CK, Elfaki I, Rehman S, Javid J, Khullar N, et al. MicroRNA-224 (rs188519172 A>G) gene variability is associated with a decreased susceptibility to Coronary Artery Disease: A Case-Control Study. MicroRNA 2018.
[http://dx.doi.org/10.2174/2211536608666181211153859] [PMID: 30539710]
[17]
Elfaki I, Almutairi FM, Mir R, Khan R. Cytochrome FA-d. P450 CYP1B1*2 gene and its association with T2D in tabuk population, northwestern region of Saudi Arabia. Asian J Pharmaceut Clin Res 2018; 11(1): 55-9.
[http://dx.doi.org/10.22159/ajpcr.2018.v11i1.21657]
[18]
Jha CK, Mir R, Elfaki I, et al. Evaluation of the association of Omentin 1 rs2274907 A>T and rs2274908 G>A gene polymorphism with coronary artery disease in indian population: a case control study. J Pers Med 2019; 9(2)E30
[http://dx.doi.org/10.3390/jpm9020030] [PMID: 31174318]
[19]
Mir R, Jha C, Elfaki I, Javid DJ, Rehman S, Khullar N, et al. Incidence of microR-4513C/T gene variability in coronary artery disease.- A case-Control Study. 2019.
[20]
Wu B, Liu G, He F, et al. miR-3188 (rs7247237-C>T) single-nucleotide polymorphism is associated with the incidence of vascular complications in chinese patients with type 2 diabetes. J Cardiovasc Pharmacol 2019; 74(1): 62-70.
[http://dx.doi.org/10.1097/FJC.0000000000000681] [PMID: 31274844]
[21]
Arjumand W, Merry CD, Wang C, et al. Phosphatidyl inositol-3 kinase (PIK3CA) E545K mutation confers cisplatin resistance and a migratory phenotype in cervical cancer cells. Oncotarget 2016; 7(50): 82424-39.
[http://dx.doi.org/10.18632/oncotarget.10955] [PMID: 27489350]
[22]
Rivière JB, Mirzaa GM, O’Roak BJ, et al. Finding of rare disease genes (FORGE) Canada consortium. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet 2012; 44(8): 934-40.
[http://dx.doi.org/10.1038/ng.2331] [PMID: 22729224]
[23]
Feng J, Xing W, Xie L. Regulatory roles of MicroRNAs in diabetes. Int J Mol Sci 2016; 17(10)E1729
[http://dx.doi.org/10.3390/ijms17101729] [PMID: 27763497]
[24]
Al Dawish MA, Robert AA, Braham R, et al. Diabetes mellitus in saudi arabia: A review of the recent literature. Curr Diabetes Rev 2016; 12(4): 359-68.
[http://dx.doi.org/10.2174/1573399811666150724095130] [PMID: 26206092]
[25]
Prasad RB, Groop L. Genetics of type 2 diabetes-pitfalls and possibilities. Genes (Basel) 2015; 6(1): 87-123.
[http://dx.doi.org/10.3390/genes6010087] [PMID: 25774817]
[26]
Almutairi FM, Mir R, Abu-Duhier F, Khan R, Harby K, Elfaki I. SLC2A2 Gene (Glucose Transporter 2) variation is associated with an increased risk of Developing T2D in an ethnic population of Saudi Arabia. Indian J Public Health Res Development 2019; 10(1): 600-5.
[http://dx.doi.org/10.5958/0976-5506.2019.00118.9]
[27]
Akinleye A, Avvaru P, Furqan M, Song Y, Liu D. Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. J Hematol Oncol 2013; 6(1): 88.
[http://dx.doi.org/10.1186/1756-8722-6-88] [PMID: 24261963]
[28]
Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 2014; 6(1)a009191
[http://dx.doi.org/10.1101/cshperspect.a009191] [PMID: 24384568]
[29]
Wang Y, Zhang H, Lin M, Wang Y. Association of FGFR2 and PI3KCA genetic variants with the risk of breast cancer in a Chinese population. Cancer Manag Res 2018; 10: 1305-11.
[http://dx.doi.org/10.2147/CMAR.S164084] [PMID: 29872343]
[30]
Ross RL, Burns JE, Taylor CF, Mellor P, Anderson DH, Knowles MA. Identification of mutations in distinct regions of p85 alpha in urothelial cancer. PLoS One 2013; 8(12)e84411
[http://dx.doi.org/10.1371/journal.pone.0084411] [PMID: 24367658]
[31]
Hakan Karadoğan A, Arikoglu H, Göktürk F, Iscioglu F, Ipekci S. PIK3R1 gene polymorphisms are associated with type 2 diabetes and related features in the Turkish population 2018.
[32]
Małodobra M. The role of single nucleotide polymorphisms of untranslated regions (Utrs) in insulin resistance pathogenesis in patients with type 2 diabetes medical complications of type 2 diabetes. IntechOpen 2011.

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