A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach.
Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investigating biosynthetic and metabolic enzymes governing the rate of 5-HT activity and their relationship to migraine, it was the objective of this study to assess genetic variants within the human tryptophan hydroxylase (TPH), amino acid decarboxylase (AADC) and monoamine oxidase A (MAOA) genes in migraine susceptibility. This objective was undertaken using a high-throughput DNA pooling experimental design, which proved to be a very accurate, sensitive and specific method of estimating allele frequencies for single nucleotide polymorphism, insertion deletion and variable number tandem repeat loci. Application of DNA pooling to a wide array of genetic loci provides greater scope in the assessment of population-based genetic association study designs. Despite the application of this high-throughput genotyping method, negative results from the two-stage DNA pooling design used to screen loci within the TPH, AADC and MAOA genes did not support their role in migraine susceptibility.
Johnson
Matthew P
MP
Genomics Research Centre, School of Medical Science, Griffith University, PMB 50 GCMC, 9726 Gold Coast, QLD, Australia.
Griffiths
Lyn R
LR
D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics; D016009:Chi-Square Distribution; D005787:Gene Frequency; D005788:Gene Pool; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008881:Migraine Disorders / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D008995:Monoamine Oxidase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics
D012701:Serotonin; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase; D001142:Aromatic-L-Amino-Acid Decarboxylases