Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

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

Research Article

Investigating Association Level of CXCL12 with its SDF-1α 3′A Genetic Variant and CXCL10 with its 1443 Promoter Polymorphism in Type-1 Diabetes

Author(s): Shokoofeh Derakhshan, Gholamhossein Hassanshahi, Mojgan Noroozi Karimabad* and Seyedeh Atekeh Torabizadeh*

Volume 19, Issue 8, 2023

Published on: 17 November, 2022

Article ID: e150922208849 Pages: 6

DOI: 10.2174/1573399819666220915120320

Price: $65

conference banner
Abstract

Background: Type-1 Diabetes Mellitus (T1DM) is an autoimmune and heterogeneous disorder. In the present study, we aimed to examine whether there exists an association between serum CXCL10 (IP-10) level and its promoter polymorphism at position-1443 along with CXCL12 and its known SDF-1 3′ A genetic variant as an angiogenesis chemokine in T1DM patients.

Methods: Blood specimens were collected from 209 unrelated T1DM patients and 189 healthy subjects. The DNA samples were extracted from the subjects and analyzed for CXCL10 and CXCL12 polymorphisms using PCR-RLFP. The serum concentrations of CXCL10 and CXCL12 were also analyzed with ELISA.

Results: Following expert opinion and data analysis, we found significant differences between A/A, A/G, and G/G genotypes with A and G alleles of polymorphisms at position +801 (SDF-1α3′A) in CXCL12. No association was reported between CXCL10/-1443 promoter polymorphism and T1DM. In our assessment of promoter polymorphism, both T1DM patients and controls had GG genotypes in CXCL10/-1443. When patients were compared with controls, both serum CXCL10 and CXCL12 levels were found to be increased in type 1 diabetes with complications. Levels were not increased in patients without complications.

Conclusion: Both CXCL10 and CXCL12 play fundamental roles in T1DM pathogenesis. Only the CXCL12 3′A (SDF-1α3′A) polymorphism is possibly necessary for the pathogenesis of T1DM, while the CXCL10-1443 promoter polymorphism is not.

Keywords: Chemokines, CXCL10, CXCL12, polymorphism, type 1 diabetes, genetic variant.

[1]
Darakhshan S, Hassanshahi G, Mofidifar Z, Soltani B, Karimabad MN. CXCL9/CXCL10 angiostasis CXC-chemokines in parallel with the CXCL12 as an angiogenesis CXC-chemokine are variously expressed in pre-eclamptic-women and their neonates. Pregnancy Hypertens 2019; 17: 36-42.
[http://dx.doi.org/10.1016/j.preghy.2019.05.001] [PMID: 31487653]
[2]
Karimabad MN, Hassanshahi G. Significance of CXCL12 in type 2 diabetes mellitus and its associated complications. Inflammation 2015; 38(2): 710-7.
[http://dx.doi.org/10.1007/s10753-014-9981-3] [PMID: 25085744]
[3]
Morran MP, Vonberg A, Khadra A, Pietropaolo M. Immunogenetics of type 1 diabetes mellitus. Mol Aspects Med 2015; 42: 42-60.
[http://dx.doi.org/10.1016/j.mam.2014.12.004] [PMID: 25579746]
[4]
Lu J, Liu J, Li L, Lan Y, Liang Y. Cytokines in type 1 diabetes: Mechanisms of action and immunotherapeutic targets. Clin Transl Immunology 2020; 9(3): e1122.
[http://dx.doi.org/10.1002/cti2.1122] [PMID: 32185024]
[5]
Darakhshan S, Fatehi A, Hassanshahi G, Mahmoodi S, Hashemi MS, Karimabad MN. Serum concentration of angiogenic (CXCL1, CXCL12) and angiostasis (CXCL9, CXCL10) CXC chemokines are differentially altered in normal and gestational diabetes mellitus associated pregnancies. J Diabetes Metab Disord 2019; 18(2): 371-8.
[http://dx.doi.org/10.1007/s40200-019-00421-2] [PMID: 31890662]
[6]
Christen U, Kimmel R. Chemokines as drivers of the autoimmune destruction in type 1 diabetes: Opportunity for therapeutic intervention in consideration of an optimal treatment schedule. Front Endocrinol (Lausanne) 2020; 11: 591083.
[http://dx.doi.org/10.3389/fendo.2020.591083] [PMID: 33193102]
[7]
Varley CL, Armitage S, Hassanshahiraviz G, Dickson AJ. Regulation of the C-X-C chemokine, mob-1, gene expression in primary rat hepatocytes. Cytokine 2003; 23(3): 64-75.
[http://dx.doi.org/10.1016/S1043-4666(03)00198-4] [PMID: 12906869]
[8]
Farangis F, Majid M, Gholamhossein H, et al. CC chemokines CCL2, CCL3, CCL4 and CCL5 are elevated in osteoporosis patients. J Biomed Res 2017; 31(5): 468-70.
[http://dx.doi.org/10.7555/JBR.31.20150166] [PMID: 28958999]
[9]
Luster AD. Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338(7): 436-45.
[http://dx.doi.org/10.1056/NEJM199802123380706] [PMID: 9459648]
[10]
Moosavi SR, Khorramdelazad H, Amin M, et al. The SDF-1 3'A genetic variation is correlated with elevated intra-tumor tissue and circulating concentration of CXCL12 in glial tumors: A study on Iranian anaplastic astrocytoma and glioblastoma multiforme patients. J Mol Neurosci 2013; 50(2): 298-304.
[http://dx.doi.org/10.1007/s12031-013-9954-2] [PMID: 23335032]
[11]
Matin K, Salam MA, Akhter J, Hanada N, Senpuku H. Role of stromal-cell derived factor-1 in the development of autoimmune diseases in non-obese diabetic mice. Immunology 2002; 107(2): 222-32.
[http://dx.doi.org/10.1046/j.1365-2567.2002.01478.x] [PMID: 12383202]
[12]
Yamada Y, Okubo Y, Shimada A, et al. Acceleration of diabetes development in CXC chemokine receptor 3 (CXCR3)-deficient NOD mice. Diabetologia 2012; 55(8): 2238-45.
[http://dx.doi.org/10.1007/s00125-012-2547-8] [PMID: 22487925]
[13]
Korbecki J, Kojder K, Kapczuk P, et al. The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors a review of literature. Int J Mol Sci 2021; 22(2): 843.
[http://dx.doi.org/10.3390/ijms22020843] [PMID: 33467722]
[14]
Dubois-Laforgue D, Hendel H, Caillat-Zucman S, et al. A common stromal cell-derived factor-1 chemokine gene variant is associated with the early onset of type 1 diabetes. Diabetes 2001; 50(5): 1211-3.
[http://dx.doi.org/10.2337/diabetes.50.5.1211] [PMID: 11334429]
[15]
Karakus S, Bagci B, Bagci G, et al. SDF-1/CXCL12 and CXCR4 gene variants, and elevated serum SDF-1 levels are associated with preeclampsia. Hypertens Pregnancy 2017; 36(2): 124-30.
[http://dx.doi.org/10.1080/10641955.2016.1250904] [PMID: 28001450]
[16]
Soriano A, Martínez C, García F, et al. Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A genotype, and expression of CXCR4 on T lymphocytes: their impact on resistance to human immunodeficiency virus type 1 infection and its progression. J Infect Dis 2002; 186(7): 922-31.
[http://dx.doi.org/10.1086/343741] [PMID: 12232832]
[17]
American Diabetes Association. Standards of medical care in diabetes--2008. Diabetes Care 2008; 31 (Suppl. 1): S12-54.
[http://dx.doi.org/10.2337/dc08-S012] [PMID: 18165335]
[18]
Kawasaki E, Ide A, Abiru N, et al. Stromal cell-derived factor-1 chemokine gene variant in patients with type 1 diabetes and autoimmune thyroid disease. Ann N Y Acad Sci 2004; 1037(1): 79-83.
[http://dx.doi.org/10.1196/annals.1337.012] [PMID: 15699497]
[19]
Karimabad MN, Khoramdelazad H, Hassanshahi G. Genetic variation, biological structure, sources, and fundamental parts played by CXCL12 in pathophysiology of type 1 diabetes mellitus. Int J Diabetes Dev Ctries 2017; 37(3): 229-39.
[http://dx.doi.org/10.1007/s13410-016-0534-1]
[20]
Winkler C, Modi W, Smith MW, et al. Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. Science 1998; 279(5349): 389-93.
[http://dx.doi.org/10.1126/science.279.5349.389] [PMID: 9430590]
[21]
Taghavi Y, Hassanshahi G, Kounis NG, Koniari I, Khorramdelazad H. Monocyte chemoattractant protein-1 (MCP-1/CCL2) in diabetic retinopathy: Latest evidence and clinical considerations. J Cell Commun Signal 2019; 13(4): 451-62.
[http://dx.doi.org/10.1007/s12079-018-00500-8] [PMID: 30607767]
[22]
Clarke DL, Clifford RL, Jindarat S, et al. TNFα and IFNγ synergistically enhance transcriptional activation of CXCL10 in human airway smooth muscle cells via STAT-1, NF-κB, and the transcriptional coactivator CREB-binding protein. J Biol Chem 2010; 285(38): 29101-10.
[http://dx.doi.org/10.1074/jbc.M109.099952] [PMID: 20833730]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy