Bi-allelic and tri-allelic 5-HTTLPR polymorphisms and triptan non-response in cluster headache

Schürks, Markus; Frahnow, Antje; Diener, Hans‐Christoph; Kurth, Tobias; Rosskopf, Dieter; Grabe, Hans‐Jörgen

doi:10.1186/1129-2377-15-46

Cited by 9 publications

(12 citation statements)

References 31 publications

(36 reference statements)

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“…However, another study suggested the splice variant is biologically inactive, since it did not modulate N-type Ca 2+ or G protein-gated inwardly rectifying K channels, unlike its wildtype counterpart in rat sympathetic neurons (104). In a genetic association study with 148 CH patients, variants in the serotonin-transporter-linked polymorphic region ( 5-HTTLPR ), a promoter region of the primary serotonin transporter, encoded by the SLC6A4 gene, which clears serotonin from the synaptic cleft, were studied by restriction fragment length polymorphism (RFLP) analysis (105). No association was found between the two variants investigated (a 43-bp indel (rs4795541), and an A > G SNP (rs25531)) with response to triptans.…”

Section: Genetics Of Cluster Headachementioning

confidence: 99%

Genetics of cluster headache

et al. 2019

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Background Cluster headache is the most severe primary headache disorder. A genetic basis has long been suggested by family and twin studies; however, little is understood about the genetic variants that contribute to cluster headache susceptibility. Methods We conducted a literature search of the MEDLINE database using the PubMed search engine to identify all human genetic studies for cluster headache. In this article we provide a review of those genetic studies, along with an overview of the pathophysiology of cluster headache and a brief review of migraine genetics, which have both been significant drivers of cluster headache candidate gene selection. Results The investigation of cluster headache genetic etiology has been dominated by candidate gene studies. Candidate selection has largely been driven by the pathophysiology, such as the striking rhythmic nature of the attacks, which spurred close examination of the circadian rhythm genes CLOCK and HCRTR2. More recently, unbiased genetic approaches such as genome-wide association studies (GWAS) have yielded new genetic avenues of interest including ADCYAP1R1 and MME. Conclusions The majority of candidate genes studied for cluster headache suffer from poor reproducibility. Broader genetic interrogation through larger unbiased GWAS, exome, and whole genome studies may provide more robust candidates, and in turn provide a clearer understanding of the causes of cluster headache.

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Section: Genetics Of Cluster Headachementioning

confidence: 99%

Genetics of cluster headache

et al. 2019

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“…The detailed flowchart of literature review process and reasons for study exclusion is shown in Figure 1. Among the 27 studies included in this review, 13–17,20–23,25,32–48 23 candidate gene association studies 13–17,20–23,32–40,42–46 and one GWAS 41 investigated the association of gene polymorphisms with CH susceptibility, whereas four studies using a candidate gene approach evaluated the association with treatment response in patients with CH 17,25,47,48 . Main participants’ characteristics, gene variants analyzed, and positive findings of the included studies are shown in Tables 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

“…Among the four studies evaluating the association between genetic variants and treatment response in patients with CH, 17,25,47,48 two studies including a total of 174 responders and 54 nonresponders investigated the association of GNB3 rs5443 with clinical response to triptans 17,25 5) showed an association of rs5443 with treatment response under the dominant genetic contrast (CT+TT vs. CC, OR: 1.96, 95% CI: 1.04–3.72, p = 0.038; Figure 5A), but not under the recessive (TT vs. CT+CC, OR: 0.38, 95% CI: 0.14–1.02, p = 0.055; Figure 5B) or the allelic contrast (T vs. C, OR: 1.20, 95% CI: 0.74–1.97, p = 0.459; Figure 5C).…”

Section: Resultsmentioning

confidence: 99%

Gene polymorphism association studies in cluster headache: A field synopsis and systematic meta‐analyses

Cargnin

Sances²,

Smıth

et al. 2021

Headache

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Background A plethora of studies have attempted to identify genetic determinants of disease susceptibility and treatment response of patients with cluster headache (CH), but results are often conflicting, and no comprehensive overview with a quantitative summary of the evidence in this field is available. Methods A systematic search of relevant publications was performed without any language restrictions on PubMed, Web of Knowledge, Cochrane Library, and OpenGrey, up to December 2020. A standardized data extraction form was used to collect relevant data from each included study. Meta‐analyses were conducted for gene polymorphisms investigated in at least two studies and the Bayesian false discovery probability (BFDP) test was applied to the pooled odds ratios (ORs) to assess the credibility of the observed associations. Results Among the 27 articles identified by the systematic review, 17 studies evaluating 12 single nucleotide polymorphisms (SNPs) were included in the quantitative data analysis. The pooled results showed no significant association with CH risk of 10 SNPs, including five SNPs of HCRTR2 (rs2653349, rs2653342, rs3122156, rs10498801, and rs3800539), two SNPs of ADH4 (rs1800759 and rs1126671), CLOCK rs1801260, and two SNPs (rs1006417 and ADCYAP1R1 rs12668955) previously identified by a genome‐wide association study (GWAS). Conversely, the pooled results revealed the association of the HCRTR2 rs9357855 A allele with a higher risk of CH (A vs. G, OR: 1.33, 95% CI: 1.04–1.72, p = 0.026), and of GNB3 rs5443 with a higher response rate of patients with CH to triptan drugs (CT+TT vs. CC, OR: 1.96, 95% CI: 1.04–3.72, p = 0.038). However, assuming a prior probability of 0.001, the respective BFDP values being higher than 0.8 (BFDPrs9357855 = 0.998; BFDPrs5443 = 0.998) revealed lack of noteworthy results. Conclusions Well‐designed GWASs and large replication studies are still needed to identify reliable genetic variants of disease susceptibility and treatment response of patients with CH.

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“…However, most of these studies include only a small number of patients and may be underpowered. The positive associations found with genetic variants in the serotonin transporter have recently not been replicated [142]. A few studies have also considered medication overuse headache as a potential pharmaco-genetic interaction and have found association between this disorder and genetic polymorphisms in the dopamine neurotransmitter system (DAT, MAOA, DRD4, DRD2) and the BDNF [143][144][145] known to predispose patients to drug abuse behaviour.…”

Section: Headachementioning

confidence: 99%