Altered Allelic Distributions of the Serotonin Transporter Gene in Migraine Without Aura and Migraine with Aura

Ogilvie, AD; Russell, Michael Bjørn; Dhall, P; Battersby, S.; Ulrich, Vibeke; Smith, CA Dale; Goodwin, G M; Harmar, Anthony J.; Olesen, Jes

doi:10.1046/j.1468-2982.1998.1801023.x

Cited by 87 publications

(84 citation statements)

References 19 publications

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“…Molecular studies for genetic polymorphisms are being carried out for a number of different applications, such as anthropological and evolutionary studies [1, 2, 3, 4, 5, 6, 7, 8, 9], genetic disorders in different populations [10, 11, 12, 13, 14, 15, 16, 17], pharmacogenomics [18, 19, 20, 21], genetic identification of ethnic groups for forensic and legal applications [22, 23, 24], genetic identification of breed/stock in animals and plants for commercial applications [25]and conservation of germ plasm and applications to crop improvement [26, 27, 28, 29]. In designing these studies, an important issue to be considered is the minimum or optimum size of random sample required so that all the alleles/genotypes at one or more loci are observed with a certain prespecified probability [26, 27, 28, 31]and for reliably estimating allele frequency distributions by statistical methods [31].…”

Section: Introductionmentioning

confidence: 99%

Sample Size Considerations in Genetic Polymorphism Studies

B-Rao¹

2001

Hum Hered

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Objectives: Molecular studies for genetic polymorphisms are being carried out for a number of different applications, such as genetic disorders in different populations, pharmacogenomics, genetic identification of ethnic groups for forensic and legal applications, genetic identification of breed/stock in animals and plants for commercial applications and conservation of germ plasm. In this paper, for a random sampling scheme, we address two questions: (A) What should be the minimum size of the sample so that, with a prespecified probability, all alleles at a given locus (or haplotypes at a given set of loci) are detected? (B) What should be the sample size so that the allele frequency distribution at a given locus (or haplotype frequency distribution at a given set of loci) is estimated reliably within permissible error limits? Methods: We have used combinatorial probabilistic arguments and Monte Carlo simulations to answer these questions. Results: We found that the minimum sample size required in case A depends mainly on the prespecified probability of detecting all alleles, while in case B, it varies greatly depending on the permissible error in estimation (which will vary with the application). We have obtained the minimum sample sizes for different degrees of polymorphism at a locus under high stringency, as well as a relaxed level of permissible error. We present a detailed sampling procedure for estimating allele frequencies at a given locus, which will be of use in practical applications. Conclusion: Since the sample size required for reliable estimation of allele frequency distribution increases with the number of alleles at the locus, there is a strong case for using biallelic markers (like single nucleotide polymorphisms) when the available sample size is about 800 or less.

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Section: Introductionmentioning

confidence: 99%

Sample Size Considerations in Genetic Polymorphism Studies

B-Rao¹

2001

Hum Hered

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“…Linkage studies of polymorphisms within the 5-HTT gene have indicated that a possible relationship exists between certain polymorphisms and susceptibility to depressive disorders (12,(16)(17)(18)(19)(20)(21)(22)(23)(24). Much interest has focused on a polymorphism within intron 2, which consists of a variable number of tandem repeats (VNTR) containing between 9 (Stin2.9), 10 (Stin2.10), and 12 (Stin2.12) copies of a 17-bp element (16)(17)(18)(19)(20). The difference in the number of copies of the repeated 17-bp element has been correlated with susceptibility to bipolar and unipolar disorder (16)(17)(18)(19)(20).…”

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confidence: 99%

“…Much interest has focused on a polymorphism within intron 2, which consists of a variable number of tandem repeats (VNTR) containing between 9 (Stin2.9), 10 (Stin2.10), and 12 (Stin2.12) copies of a 17-bp element (16)(17)(18)(19)(20). The difference in the number of copies of the repeated 17-bp element has been correlated with susceptibility to bipolar and unipolar disorder (16)(17)(18)(19)(20). However, several other studies have produced data that seem to indicate that no link exists between 5-HTT intron 2 polymorphic regions and susceptibility to affective disorders (25,26).…”

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A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo

MacKenzie

Quinn

1999

Proc. Natl. Acad. Sci. U.S.A.

340

236

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Polymorphic regions consisting of a variable number of tandem repeats within intron 2 of the gene coding for the serotonin transporter protein 5-HTT have been associated with susceptibility to affective disorders. We have cloned two of these intronic polymorphisms, Stin2.10 and Stin2.12, into an expression vector containing a heterologous minimal promoter and the bacterial LacZ reporter gene. These constructs were then used to produce transgenic mice. In embryonic day 10.5 embryos, both Stin2.10 and Stin2.12 produced consistent ␤-galactosidase expression in the embryonic midbrain, hindbrain, and spinal cord floor plate. However, we observed that the levels of ␤-galactosidase expression produced by both the Stin2.10 and Stin2.12 within the rostral hindbrain differed significantly at embryonic day 10.5. Our data suggest that these polymorphic variable number of tandem repeats regions act as transcriptional regulators and have alleledependent differential enhancer-like properties within an area of the hindbrain where the 5-HTT gene is known to be transcribed at this stage of development.transcriptional regulation ͉ promoter ͉ transgenic mice ͉ LacZ gene ͉ rostral hindbrain

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“…On the other hand, clinical and experimental data from several laboratories clearly indicate that the 5-HTT gene is one of the genetically contributing factors of migraine (Murphy et al, 2001). In migraine patients with and without aura it has been shown an altered allelic division of the 5-HTT (Ogilvie et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

Nagy-Grócz

Bohár

Fejes-Szabó

et al. 2017

Journal of Chemical Neuroanatomy

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serotonin transporter expression in rat spinal cord but anandamide modulated this effect.Journal of Chemical Neuroanatomy http://dx.doi.org/10. 1016/j.jchemneu.2017.06.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Migraine is one of the most prevalent neurological diseases, which affects 16% of the total population. The exact pathomechanism of this disorder is still not well understood, but it seems that serotonin and its transporter has a crucial role in the pathogenesis.One of the animal models of migraine is the systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor. NO can initiate a central sensitization process in the trigeminal system, which is also present in migraineurs.Recent studies showed that the endocannabinoid system has a modulatory role on the trigeminal activation and sensitization.Our aim was to investigate the effect of an endogenous cannabinoid, anandamide (AEA) on the NTG-induced changes on serotonin transporter (5-HTT) expression in the upper cervical spinal cord (C1-C2) of the rat, where most of the trigeminal nociceptive afferents convey.The animals were divided into four groups. Rats in the first group, called placebo, received only the vehicle solution as treatment. In the second group, they were treated with an intraperitoneal (i.p.) injection of NTG (10mg/kg). Rats in the third and fourth groups received i.p. AEA (2x5mg/kg) half hour before and one hour after the placebo or NTG treatment. Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.Our results show that both NTG and AEA alone are able to increase 5-HTT expression in the C1-C2 segments. Combination of NTG and AEA has an opposing effect on this marker, nullifying the effects of non-combined administration, probably by negative feedback mechanisms.

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Altered Allelic Distributions of the Serotonin Transporter Gene in Migraine Without Aura and Migraine with Aura

Cited by 87 publications

References 19 publications

Sample Size Considerations in Genetic Polymorphism Studies

Sample Size Considerations in Genetic Polymorphism Studies

A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo

Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

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