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The impact of COMT, BDNF and 5-HTT brain-genes on the development of anorexia nervosa: a systematic review

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Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity Aims and scope Submit manuscript

Abstract

Purpose

The genetic aspect of anorexia nervosa (AN) involving specific genes of the central-nervous-system has not yet been clearly understood. The aim of this systematic review is to assess the impact of three candidate genes of the brain: catechol-O-methyltransferase, brain-derived neurotrophic factor (BDNF) and serotonin transporter protein, on the susceptibility to AN and identify whether a clear connection persists between each of the gene-polymorphisms and AN.

Methods

A total of 21 articles were selected for this review conforming to the PRISMA guidelines. Detailed keyword combinations were implemented within specific databases such as MEDLINE, SCIENCEDIRECT and PUBMED.

Results

The catechol-O-methyltransferase gene-polymorphism did not show any change in phenotypic variation between AN and control subjects; but the familial association was rather strong with an over-transmission of the H allele. The latter also correlated with several dimensions of the Temperament and Character Inventory (TCI) scale. A notable relation was indicated between BDNF gene-polymorphism and anorexia-restrictive in terms of phenotypic distribution; the Met66-allele also depicted high association with anorexic behavioral traits. The 5-HTTLPR gene-polymorphism was found to be significantly associated with AN susceptibility with an over-transmission of the S-allele from parents to offspring.

Conclusion

The systematic review distinctively emphasized the genetic contribution of the brain-genes on the development of AN. Despite significant study findings, no clear and standardized genetic route was determined to be the cause of AN development. Future research is needed on these specific genes to closely monitor the genetic polymorphisms and their mechanism on AN susceptibility.

Level of evidence:

I, systematic review

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Acknowledgements

We would like to express our gratitude and appreciation to University College London Libraries for supporting this review project.

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Authors and Affiliations

  1. Dietetic Department, Saint George Hospital University Medical Center, Beirut, Lebanon

    Sirine Abou Al Hassan

  2. Division of Medicine, Eating Disorders and Clinical Nutrition, University College London, London, UK

    Sirine Abou Al Hassan & Darren Cutinha

  3. Nutrition Division, Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

    Lama Mattar

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  1. Sirine Abou Al Hassan
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  2. Darren Cutinha
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  3. Lama Mattar
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Correspondence to Lama Mattar.

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Appendix: Definitions

Appendix: Definitions

ARMS assay Amplification refractory manipulation system-technique used for the detection of single base mutations or deletions [71].

Codon a sequence of 3 nucleotides from DNA or RNA that encodes for a specific amino acid during protein synthesis [72].

Cooperativeness Character dimension of the TCI scale. The extent to which an individual is empathetic, helpful and thoughtful of others [73].

Exome sequencing Method through which genetic variations are detected and identified within the protein-coding region [74].

Exome the part of the human genome that is made up of exons. Exons form 1% of the total genome and constitute the DNA sequences that encode for the specific proteins. Hence their function of protein-coding genes [74].

Genome sequencing Genetic method for the identification of genetic variations and mutation within the whole set of DNA in the human body [76].

Genome the whole genetic material of an individual that contains the complete set of genetic instructions needed for adequate growth and development. It is the full set of DNA including the genes (coding sequences) and the non-coding regions [76].

Haplotype the combination of alleles aligned within one single chromosome and inherited as unit from one of the parents. Haplotypes enable the detection of major informational change within the DNA sequences during cell division, which consequently enhances the identification of disease-causing mutations.

Harm avoidance Temperament dimension of the TCI scale. The degree to which an individual is pessimistic, constantly doubtful, worrying and fearful [73].

Heritability the proportion of variation in a specific phenotypic trait that accounts from genetic variations between individuals within the population [5].

PCR–RFLP Polymerase Chain Reaction-Restriction Fragment Length Polymorphism- Method by which a homologous DNA sample is broken down by restrictive enzymes, thus forming DNA restriction fragments. The latter are then separated using a specific gel to be analyzed for identification of the genome mapping, disease risk and genetic mutations [77].

Reward dependence Temperament dimension of the TCI scale. The extent to which one is socially attached and dependent on being approved and accepted by others [73].

Salting out procedure DNA purification method whereby a high concentration of salt is used in a sample. The water molecules would attract water molecules due to the salt ions, which become unavailable for interaction with other charged proteins. Consequently, the protein and other contaminants precipitate, which facilitates their removal from the sample for purification [78].

Self-directedness Character dimension of the TCI scale. The degree to which an individual is self-confident, self-accepting and able to control and regulate his/her behavior [73].

Synergy The idea that the interaction between combined parts would yield greater results and outcomes than if introduced separately [79].

Transmission disequilibrium test (TDT) It evaluates parents who are heterozygous for a particular allele linked to a specific disease and assesses the frequency of transmission of the allele or its polymorphism to their affected offspring [80]. Normally, a random transmission of alleles is expected with 50% transmission from each parent. However, in disease states, such as AN, a specific allele locus is associated with the particular disease condition (AN); it is therefore projected to have an over-transmission of a specific risk-allele in the AN patient population [81].

Hardy Weinberg equilibrium (HWE) A gold-standard principle stating that the genetic variation within a population, specifically the genotypic and allelic frequencies, will remain constant from one generation to the other assuming that no evolutionary factors will disrupt the equilibrium [82]. The reliance on the HWE and statistical tests for associations within studies accentuates the relevance of genetic findings and induces more credibility.

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Abou Al Hassan, S., Cutinha, D. & Mattar, L. The impact of COMT, BDNF and 5-HTT brain-genes on the development of anorexia nervosa: a systematic review. Eat Weight Disord 26, 1323–1344 (2021). https://doi.org/10.1007/s40519-020-00978-5

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