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Two-stage case-control association study of dopamine-related genes and migraine.

ABSTRACT: BACKGROUND: We previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in migraine with aura. Herein we investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission. METHODS: We performed a two-stage case-control association study of 50 tag single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters. The first analysis consisted of 263 patients and 274 controls and the replication study was composed by 259 cases and 287 controls. All cases were diagnosed according to ICHD-II criteria, were Spanish Caucasian, and were sex-matched with control subjects. RESULTS: Single-marker analysis of the first population identified nominal associations of five genes with migraine. After applying a false discovery rate correction of 10%, the differences remained significant only for DRD2 (rs2283265) and TH (rs2070762). Multiple-marker analysis identified a five-marker T-C-G-C-G (rs12363125-rs2283265-rs2242592-rs1554929-rs2234689) risk haplotype in DRD2 and a two-marker A-C (rs6356-rs2070762) risk haplotype in TH that remained significant after correction by permutations. These results, however, were not replicated in the second independent cohort. CONCLUSION: The present study does not support the involvement of the DRD1, DRD2, DRD3, DRD5, DBH, COMT, SLC6A3 and TH genes in the genetic predisposition to migraine in the Spanish population.

SUBMITTER: Corominas R

PROVIDER: S-EPMC2758864 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Two-stage case-control association study of dopamine-related genes and migraine.

Corominas Roser R Ribases Marta M Camiña Montserrat M Cuenca-León Ester E Pardo Julio J Boronat Susana S Sobrido María-Jesús MJ Cormand Bru B Macaya Alfons A

BMC medical genetics 20090921

<h4>Background</h4>We previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in migraine with aura. Herein we investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission.<h4>Methods</h4>We performed a two-stage case-control association study of 50 tag single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters. The first analy ...[more]

PMID: 19772578

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Project description:Age-related macular degeneration is the most prevalent form of visual impairment and blindness in developed countries. Genetic studies have made advancements in establishing the molecular cause of this disease, identifying mutations in the complement factor H (CFH) gene and a locus on chromosome 10 encompassing the HTRA1/LOC387715/ARMS2 genes. Variants in complement 3 (C3) and an HLA locus containing both factor B and C2 genes have also been implicated. We aimed to identify further genetic risk factors for this disease.We used a case-control study design in a UK sample of patients with age-related macular degeneration (n=479) and controls (n=479) and undertook a low-density screen of 32 genes using 93 single nucleotide polymorphisms (SNPs). Genes were selected as candidates on the basis of potential functional relevance to age-related macular degeneration. Significant initial findings were confirmed by replication in an independent US cohort of 248 unrelated patients with disease and 252 controls, and by high-density genotyping around association signals.The SNP variant rs2511989, located within intron six of the SERPING1 gene, showed highly significant genotypic association with age-related macular degeneration (uncorrected p=4.0x10(-5), corrected p=0.00372). We detected no evidence for association between disease and the other 31 candidate genes. The odds ratio for age-related macular degeneration in rs2511989 G/A heterozygotes compared with wild type G/G homozygotes was 0.63 (95% CI 0.47-0.84). A similar comparison of the A/A homozygotes with the wild type yielded an odds ratio of 0.44 (0.31-0.64). We replicated the observed genotypic association in a US cohort (p=0.008). Furthermore, a secondary high-density genotyping study across the SERPING1 gene region identified five additional SNP variants similarly associated with age-related macular degeneration (rs2244169, rs2511990, rs2509897, rs1005510, and rs2511988).Genetic variation in SERPING1 significantly alters susceptibility to age-related macular degeneration. SERPING1 encodes the C1 inhibitor, which has a crucial role in inhibition of complement component 1 (C1) and might implicate the classic pathway of complement activation in this disease.

Project description:Infantile regurgitation is one of the most common discomforts in the first months of life. Infantile colic and, in older children, functional dyspepsia have been linked to migraine. To date, this is the first study to investigate a possible association between infantile regurgitation and primary headaches in children. This is a case-control study of 195 children aged 6-17 years, with primary headache (migraine, or tension type headache) in 5 European paediatric hospitals. The control group is composed of 240 same-aged children attending with minor injuries during the same period - February 1st 2020 to December 1st 2020. A structured questionnaire identified a history of infantile regurgitation and other functional gastrointestinal disorders for case and control participants. The outcome was the difference in the prevalence of infantile regurgitation among children with or without a diagnosis of primary headache. The analysis showed a significant association between infantile regurgitation and migraine (OR = 1.88, CI 95 = 1.01-3.4, p = 0.04). No association was found between infantile regurgitation and tension type headache (p = 0.33). Subgroup analysis confirmed that the association was only significant for migraine without aura (OR = 2.3, CI 95 = 1.2-4.4, p = 0.01). In a further subgroup analysis, the presence of functional dyspepsia, irritable bowel syndrome and abdominal migraine was associated with migraine without aura.ConclusionThe presence of migraine among children aged 6-17 was associated with a history of infantile regurgitation. Additional longitudinal studies are required to confirm whether infantile regurgitation could be considered as a precursor of migraine.What is known• Children suffering from functional gastrointestinal disorders are more likely to be suffering from migraine and tension-type headache as well. • Children suffering from primary headache are more likely to have had infantile colic in their first six month of life.What is new• It is the first study to find an association between migraine and infantile regurgitation in children. • These findings could have an impact on the diagnosis and therapeutics of both migraine and infantile regurgitation.

Dataset Information

Two-stage case-control association study of dopamine-related genes and migraine.

Publications

Two-stage case-control association study of dopamine-related genes and migraine.

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