Methylation level of CNR1 in peripheral blood of children with autism spectrum disorder

WANG Feng; LIU Zehui; ZHANG Yilin; TIAN Wenru; YANG Lingyuan; ZOU Mingyang; SUN Caihong

doi:10.11852/zgetbjzz2023-0686

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Chinese Journal of Child Health Care ›› 2024, Vol. 32 ›› Issue (3) : 237-241. DOI: 10.11852/zgetbjzz2023-0686

Original Articles

Methylation level of CNR1 in peripheral blood of children with autism spectrum disorder

WANG Feng, LIU Zehui, ZHANG Yilin, TIAN Wenru, YANG Lingyuan, ZOU Mingyang, SUN Caihong

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Abstract

Objective To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. Methods A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. Results The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P＜0.05). Conclusions The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

Key words

autism spectrum disorder / CNR1 gene / methylation / social interaction disorder

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WANG Feng, LIU Zehui, ZHANG Yilin, TIAN Wenru, YANG Lingyuan, ZOU Mingyang, SUN Caihong. Methylation level of CNR1 in peripheral blood of children with autism spectrum disorder[J]. Chinese Journal of Child Health Care. 2024, 32(3): 237-241 https://doi.org/10.11852/zgetbjzz2023-0686

References

[1] Maenner MJ, Warren Z, Williams AR, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years-Autism and developmental disabilities monitoring network, 11 sites, United States, 2020[J]. MMWR Surveill Summ, 2023, 72(2): 1-14.
[2] Srancikova A, Bacova Z, Bakos J. The epigenetic regulation of synaptic genes contributes to the etiology of autism[J]. Rev Neurosci, 2021, 32(7): 791-802.
[3] Levy MA, Relator R, Mcconkey H, et al. Functional correlation of genome-wide DNA methylation profiles in genetic neurodevelopmental disorders[J]. Hum Mutat, 2022, 43(11): 1609-1628.
[4] Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome[J]. Cell, 1991, 65(5): 905-914.
[5] Fyke W, Premoli M, Echeverry Alzate V, et al. Communication and social interaction in the cannabinoid-type 1 receptor null mouse: Implications for autism spectrum disorder[J]. Autism Res, 2021, 14(9): 1854-1872.
[6] Lutz B. Neurobiology of cannabinoid receptor signaling[J]. Dialogues Clin Neuro, 2022, 22(3): 207-222.
[7] Crittenden JR, Yoshida T, Venu S, et al. Cannabinoid receptor 1 is required for neurodevelopment of striosome-dendron bouquets[J]. eNeuro, 2022, 9(2):ENERO.0318-21.2022.
[8] Zou M, Li D, Li L, et al. Role of the endocannabinoid system in neurological disorders[J]. Int J Dev Neurosci, 2019, 76: 95-102.
[9] Forte N, Boccella S, Tunisi L, et al. Orexin-A and endocannabinoids are involved in obesity-associated alteration of hippocampal neurogenesis, plasticity, and episodic memory in mice[J]. Nat Commun, 2021, 12(1): 6137.
[10] Sitzia G, Abrahao KP, Liput D, et al. Distinct mechanisms of CB1 and GABA(B) receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus[J]. J Physiol, 2023, 601(1): 195-209.
[11] Palmisano M, Gargano A, Olabiyi BF, et al. Hippocampal deletion of cB1 receptor impairs social memory and leads to age-related changes in the hippocampus of adult mice[J]. Int J Mol Sci, 2022, 24(1):26.
[12] D'addario C, Micale V, Di Bartolomeo M, et al. A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia[J]. Schizophr Res, 2017, 188: 132-140.
[13] Yang C, Nolte IM, Ma Y, et al. The associations of CNR1 SNPs and haplotypes with vulnerability and treatment response phenotypes in Han Chinese with major depressive disorder: A case-control association study[J]. Mol Genet Genomic Med, 2021, 9(9): e1752.
[14] Zou M, Liu Y, Xie S, et al. Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder[J]. Open Biol, 2021, 11(2): 200306.
[15] Zamberletti E, Gabaglio M, Piscitelli F, et al. Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male Mecp2 mutant mice[J]. J Psychopharmacol, 2019, 33(7): 894-907.
[16] Gould GG, Burke TF, Osorio MD, et al. Enhanced novelty-induced corticosterone spike and upregulated serotonin 5-HT1A and cannabinoid CB1 receptors in adolescent BTBR mice[J]. Psychoneuroendocrinology, 2014, 39: 158-169.
[17] Straiker A, Min KT, Mackie K. Fmr1 deletion enhances and ultimately desensitizes CB(1) signaling in autaptic hippocampal neurons[J]. Neurobiol Dis, 2013, 56: 1-5.
[18] Behl T, Chadha S, Sachdeva M, et al. Understanding the possible role of endocannabinoid system in obesity[J]. Prostaglandins Other Lipid Mediat, 2021, 152: 106520.
[19] Chakrabarti B, Baron-Cohen S. Variation in the human cannabinoid receptor CNR1 gene modulates gaze duration for happy faces[J]. Mol Autism, 2011, 2(1): 10.
[20] Gonczarowska N, Tomaz C, Caixeta FV, et al. CB1 receptor antagonism in capuchin monkeys alters social interaction and aversive memory extinction[J]. Psychopharmacology (Berl), 2019, 236(12): 3413-3419.
[21] Wei D, Dinh D, Lee D, et al. Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment[J]. Cannabis Cannabinoid Res, 2016, 1(1): 81-89.
[22] Poleg S, Kourieh E, Ruban A, et al. Behavioral aspects and neurobiological properties underlying medical cannabis treatment in Shank3 mouse model of autism spectrum disorder[J]. Transl Psychiatry, 2021, 11(1): 524.
[23] De Giacomo V, Ruehle S, Lutz B, et al. Cell type-specific genetic reconstitution of CB1 receptor subsets to assess their role in exploratory behaviour, sociability, and memory[J]. Eur J Neurosci, 2022, 55(4): 939-951.
[24] Tammen SA, Friso S, Choi SW. Epigenetics:The link between nature and nurture[J]. Mol Aspects Med, 2013, 34(4): 753-764.