An Investigation of SDF1/CXCR4 Gene Polymorphisms in Autism Spectrum Disorder: A Family-Based Study
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Objective Autism spectrum disorders (ASD) have a complex pathophysiology including genetic, inflammatory and neurodevelopmental components. We aim to investigate the relationship between ASD and gene polymorphisms of stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor-4 (CXCR4), which may affect inflammatory and neurodevelopmental processes. Methods 101 children diagnosed with ASD aged 2–18 and their biological parents were included in the study. All participants were assessed using an information form and the Children were assessed using Childhood Autism Rating Scale (CARS). SDF-1 G801→A and CXCR4 C13→T polymorphisms were detected by genetic techniques. The results were evaluated using the transmission disequilibrium test (TDT) and haplotype relative risk (HRR). Results Following TDT evaluation for CXCR4, the assumption of equality was not rejected (χ2=1.385, p=0.239). HRR for the C allele was 1.037 [HRR (95%CI)=0.937 (0.450–2.387), χ2=0.007, p=0.933] and HRR for the T allele was 0.965 [HRR (95%CI)=0.965 (0.419– 2.221), χ2=1.219, p=0.270], but the findings were statistically insignificant. Based on TDT evaluation for SDF1, the assumption of equality cannot be rejected (χ2=0, p=0.999). HRR for the A allele was 0.701 [HRR (95%CI)=0.701 (0.372–1.319), χ2=1.219, p=0.270] and HRR for the G allele was 1.427 [HRR (95%CI)=1.427 (0.758–2.686), χ2=1.219, p=0.270], but the findings were statistically insignificant. Conclusion The genetic screening of blood samples from mother, father and child trios could not show a significant association between SDF1/CXCR4 genes and ASD on the basis of TDT and HRR tests. More extensive genetic studies are now needed to investigate the relationship between SDF1/CXCR4 gene polymorphisms and ASD.
Abstract
Objective Autism spectrum disorders (ASD) have a complex pathophysiology including genetic, inflammatory and neurodevelopmental components. We aim to investigate the relationship between ASD and gene polymorphisms of stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor-4 (CXCR4), which may affect inflammatory and neurodevelopmental processes. Methods 101 children diagnosed with ASD aged 2–18 and their biological parents were included in the study. All participants were assessed using an information form and the Children were assessed using Childhood Autism Rating Scale (CARS). SDF-1 G801→A and CXCR4 C13→T polymorphisms were detected by genetic techniques. The results were evaluated using the transmission disequilibrium test (TDT) and haplotype relative risk (HRR). Results Following TDT evaluation for CXCR4, the assumption of equality was not rejected (χ2=1.385, p=0.239). HRR for the C allele was 1.037 [HRR (95%CI)=0.937 (0.450–2.387), χ2=0.007, p=0.933] and HRR for the T allele was 0.965 [HRR (95%CI)=0.965 (0.419– 2.221), χ2=1.219, p=0.270], but the findings were statistically insignificant. Based on TDT evaluation for SDF1, the assumption of equality cannot be rejected (χ2=0, p=0.999). HRR for the A allele was 0.701 [HRR (95%CI)=0.701 (0.372–1.319), χ2=1.219, p=0.270] and HRR for the G allele was 1.427 [HRR (95%CI)=1.427 (0.758–2.686), χ2=1.219, p=0.270], but the findings were statistically insignificant. Conclusion The genetic screening of blood samples from mother, father and child trios could not show a significant association between SDF1/CXCR4 genes and ASD on the basis of TDT and HRR tests. More extensive genetic studies are now needed to investigate the relationship between SDF1/CXCR4 gene polymorphisms and ASD.
참고문헌 (40)
- Coucouvanis J, "Autism Spectrum Disorder;Child and Adolescent Behavioral Health", pp.238~261 (2012), John Wiley & Sons, Ltd
- Casanova MF, "Neuroscience of Autism;Psychiatry, 4th Ed", pp.382~397 (2015), John Wiley & Sons, Ltd.
- Ann Le Couteur, "Autism spectrum disorder;Rutter's Child and Adolescent Psychiatry, 6th Ed", pp.661~682 (2015), John Wiley & Sons, Ltd
- Dembic Z, "Chemokines;Cytokines of the Immune System", pp.241~262 (2015), Academic Press
- Murdoch C, "Functional expression of chemokine receptor CXCR4 on human epithelial cells", Immunology, 98, pp.36~41 (1999)[DOI]
- Adler MW, "Viewing chemokines as a third major system of communication in the brain", AAPS J, 7, pp.865~870 (2005)[DOI]
- Lopez-Bendito G, "Chemokine signaling controls intracortical migration and final distribution of GABAergic interneurons", J Neurosci, 28, pp.1613~1624 (2008)[DOI]
- Banisadr G, "Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons", Eur J Neurosci, 16, pp.1661~1671 (2002)[DOI]
- Ijsbrand Kramer M, "Chemokines and Traffic of White Blood Cells;Signal Transduction, 3rd Ed", pp.777~812 (2016), Academic Press
- Krakowiak P, "Neonatal cytokine profiles associated with autism spectrum disorder", Biol Psychiatry, 81, pp.442~451 (2017)[DOI]
- Zerbo O, "Neonatal cytokines and chemokines and risk of Autism Spectrum Disorder: the Early Markers for Autism (EMA) study: a case-control study", J Neuroinflammation, 11, pp.113~ (2014)[DOI]
- Cash-Padgett T, "Increased stereotypy in conditional Cxcr4 knockout mice", Neurosci Res, 105, pp.75~79 (2016)[DOI]
- Uppal N, "A Stereologic Perspective on Autism Neuropathology;Neurostereology: Unbiased Stereology of Neural Systems", pp.237~256 (2014), John Wiley & Sons, Inc
- Betancur C, "Synaptic Disorders;The Genetics of Neurodevelopmental Disorders", pp.195~238 (2015), John Wiley & Sons, Inc
- Meechan, "Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome", Proc Natl Acad Sci US, 109, pp.18601~18606 (2012)[DOI]
- Shi MD, "CXCL12-G801A polymorphism modulates risk of colorectal cancer in Taiwan", Arch Med Sci, 9, pp.999~1005 (2013)
- Okuyama Kishima M, "Genetic polymorphism and expression of CXCR4 in breast cancer", Anal Cell Pathol (Amst), 2015, pp.289510~ (2015)
- Mackay CR, "Chemokines: immunology's high impact factors", Nat Immunol, 2, pp.95~101 (2001)[DOI]
- Bacon KB, "Chemokines and their receptors in neurobiology: perspectives in physiology and homeostasis", J Neuroimmunol, 104, pp.92~97 (2000)[DOI]
- Jiang Y, "Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis", J Neuroimmunol, 86, pp.1~12 (1998)[DOI]
- Siebert H, "The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system", J Neuroimmunol, 110, pp.177~185 (2000)[DOI]
- Ma Q, "Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice", Proc Natl Acad Sci USA, 95, pp.9448~9453 (1998)[DOI]
- Arimitsu N, "Role of SDF1", CXCR4 interaction in experimental hemiplegic models with neural cell transplantation, 2012, pp.13, 2636~2649
- Madison JM, "Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities", Mol Psychiatry, 20, pp.703~717 (2015)[DOI]
- Ashwood P, "Is autism an autoimmune disease?", Autoimmun Rev, 3, pp.557~562 (2004)[DOI]
- Suzuki K, "Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders", PLoS ONE, 6, pp.e20470~ (2011)[DOI]
- Abdallah MW, "Neonatal chemokine levels and risk of autism spectrum disorders: findings from a Danish historic birth cohort follow-up study", Cytokine, 61, pp.370~376 (2013)[DOI]
- Ashwood P, "Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders", J Neuroimmunol, 232, pp.196~199 (2011)[DOI]
- Isman FK, "Association between SDF1-3'A or CXCR4 gene polymorphisms with predisposition to and clinicopathological characteristics of prostate cancer with or without metastases", Mol Biol Rep, 39, pp.11073~11079 (2012)[DOI]
- Lee YL, "Association of genetic polymorphisms of CXCL12", SDF1 gene and its receptor, CXCR4, to the susceptibility and prognosis of non-small cell lung cancer, 2011, pp.73, 147~152
- Ide A, "Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population", Hum Immunol, 64, pp.973~978 (2003)[DOI]
- Kim YJ, "LAMB1 polymorphism is associated with autism symptom severity in Korean autism spectrum disorder patients", Nord J Psychiatry, 69, pp.594~598 (2015)[DOI]
- Schmidt RJ, "Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study", Early Hum Dev, 91, pp.483~489 (2015)[DOI]
- Sesarini CV, "Association between GABA(A) receptor subunit polymorphisms and autism spectrum disorder (ASD)", Psychiatry Res, 229, pp.580~582 (2015)[DOI]
- Saxena V, "Structural, genetic, and functional signatures of disordered neuro-immunological development in autism spectrum disorder", PLoS One, 7, pp.e48835~ (2012)[DOI]
- Shailesh H, "Towards understanding the genetics of Autism", Front Biosci (Elite Ed), 8, pp.412~426 (2016)
- 조수철, "Genome-Wide Association Scan of Korean Autism Spectrum Disorders with Language Delay: A Preliminary Study", PSYCHIATRY INVESTIGATION, 8(1), pp.61~66 (2011), 대한신경정신의학회
- Sweeten TL, "High blood monocyte counts and neopterin levels in children with autistic disorder", Am J Psychiatry, 160, pp.1691~1693 (2003)[DOI]
- Torres AR, "The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder", Hum Immunol, 63, pp.311~316 (2002)[DOI]
- O'Donovan MC, "Candidate-gene association studies of schizophrenia", Am J Hum Genet, 65, pp.587~592 (1999)[DOI]