Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population

Papasavva, Maria; Katsarou, Martha‐Spyridoula; Vikelis, Michail; Mitropoulou, Euthymia; Dermitzakis, Emmanouil V.; Papakonstantinou, Stylianos; Arvaniti, Chrysa; Mitsikostas, Dimos‐Dimitrios; Gozes, Illana; Tsatsakis, Aristidis; Drakoulis, Nikolaos

doi:10.1007/s12031-019-01439-0

Cited by 11 publications

(33 citation statements)

References 54 publications

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“…Weller et al [2015] found no evidence for association between rs2653349 polymorphism in the HCRTR2 gene and CH. This result is in agreement with studies performed in Sweden (Fourier et al, 2019), Southeastern European (Papasavva et al, 2020), and China (Fan et al, 2018). The possible reasons for negative results could be as follows: First, the results of previous published literature may be overestimated due to the limited sample size or different populations.…”

Section: Discussionsupporting

confidence: 90%

“…Among the remaining 11 articles, 1 was considered unrelated based on predefined inclusion and exclusion criteria and was removed, and 2 were excluded because of duplicated data. Ultimately, eight articles (Baumber et al, 2006;Schürks et al, 2006;Rainero et al, 2008;Weller et al, 2015;Zarrilli et al, 2015;Fan et al, 2018;Fourier et al, 2019;Papasavva et al, 2020) were included in the systematic review and meta-analysis. Figure 2 shows the process of literature selection.…”

Section: Literature Searchmentioning

confidence: 99%

“…All the articles were published in English between 2006 and 2020. One of the studies was carried out in China (Fan et al, 2018); two in Italy (Rainero et al, 2008;Zarrilli et al, 2015); one in the UK, Denmark, and Sweden (Baumber et al, 2006); one in Sweden (Fourier et al, 2019); one in Greece (Papasavva et al, 2020); one in Germany (Schürks et al, 2006); and one in the Netherlands (Weller et al, 2015). All the studies were conducted in Caucasian populations, expect one in Asian populations (Fan et al, 2018).…”

Section: Literature Searchmentioning

confidence: 99%

“…Many genes with a huge number of gene polymorphisms have been classified to have covert risk alleles for CH susceptibility and vulnerability. Presently, G protein beta 3 subunit (GNB3) (Papasavva et al, 2020), alcohol dehydrogenase 4 (ADH4) (Fourier et al, 2016), and various candidate genes like hypocretin receptor type 2 (HCRTR2) (Fourier et al, 2019;Papasavva et al, 2020) have been widely reported to be related to CH. Figure 1 shows the HCRTR2 protein-protein interaction (PPI) network and its closest functional protein partners.…”

Section: Introductionmentioning

confidence: 99%

“…Figure 1 shows the HCRTR2 protein-protein interaction (PPI) network and its closest functional protein partners. From the figure, a few proteins that interact and collaborate with HCRTR2 are also associated with the pathogenesis of CH, including GNB3 (Papasavva et al, 2020), neuropeptide FF-amide peptide (NPFF) Abbreviations: HCRTR2, hypocretin receptor type 2; CH, cluster headache; NOS, Newcastle-Ottawa Scale; ICHD-III, International Classification of Headache Disorders, 3rd edition; GNB3, G protein beta3 subunit; ADH4, alcohol dehydrogenase 4; PPI, protein-protein interaction; NPFF, neuropeptide FF-amide peptide; HCRT, hypocretin; ICHD-II, International Classification of Headache Disorders, 2nd edition; ICHD-III beta, International Classification of Headache Disorders; HWE, Hardy-Weinberg equilibrium.…”

Section: Introductionmentioning

confidence: 99%

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No Association Between G1246A Polymorphism in HCRTR2 Gene and Risk of Cluster Headache: Evidence From an Updated Meta-Analysis of Observational Studies

Yang

et al. 2020

Front. Genet.

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Background: The hypocretin receptor 2 (HCRTR2) gene may play a pathological role in cluster headache (CH). However, the conclusions of published reports on the relationship between the G1246A polymorphism (rs2653349) in the HCRTR2 gene and risk of CH remain controversial. This purpose of this article is to comprehensively study the current evidence and assess the association between G1246A polymorphism (rs2653349) in the HCRTR2 gene and risk of CH.Materials and Methods: Four electronic databases—ISI Web of Science, CNKI, PubMed, and EMBASE—were comprehensively searched on August 2020 to find and pinpoint all observational articles related to this study. The association between G1246A polymorphism in the HCRTR2 gene and risk of CH under five different genetic models was evaluated based on the summary odds ratio and corresponding 95 confidence interval (95% CI). Methodological quality was assessed based on the Newcastle–Ottawa Scale (NOS). To assist the analysis, RevMan 5.3 software was used to perform subgroup and sensitivity analyses. Egger's and Begg's tests were then conducted to evaluate and assess publication bias. Finally, a meta-regression was carried out by residual (restricted) maximum likelihood (REML).Results: Eight observation studies containing 3,161 healthy controls and 1,964 patients with CH were identified and to be used for the meta-analysis. With methodological quality NOS assessment, the incorporated studies showed an average score of 6.4 stars. The pooled data didn't support the association between G1246A polymorphism in the HCRTR2 gene and CH vulnerability in the overall population (OR: 0.85, 95% CI 0.69, 1.03; p = 0.10). Subgroup analysis by ethnicity showed no significant association between G1246A and CH in either Caucasians (OR: 0.89, 95% CI 0.77, 1.01; p = 0.08) or Asians (OR: 1.65, 95% CI 0.80, 3.41; p = 0.18). The robustness of the conclusion was tested and confirmed with the leave-one-out sensitivity analysis. Meta-regression analysis showed that chronological order of publication appeared to be significantly associated with the heterogeneity (t = 2.47, p = 0.039; residual I2 = 0%, adjusted R2 = 100%).Conclusion: Our present study showed that the G1246A polymorphism in the HCRTR2 gene did not appear to be an accomplice and associated with CH predisposition among either the Asian or Caucasian population.

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Section: Discussionsupporting

confidence: 90%

Section: Literature Searchmentioning

confidence: 99%

Section: Literature Searchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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No Association Between G1246A Polymorphism in HCRTR2 Gene and Risk of Cluster Headache: Evidence From an Updated Meta-Analysis of Observational Studies

Yang

et al. 2020

Front. Genet.

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Family History of Cluster Headache

et al. 2020

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IMPORTANCE Genetic and environmental factors are thought to contribute to cluster headache, and cluster headache can affect multiple members of a family. A thorough understanding of its inheritance is critical to understanding the pathogenesis of this debilitating disease.OBJECTIVE To systematically review family history rates and inheritance patterns of cluster headache.EVIDENCE REVIEW A systematic review was performed in PubMed, Embase, and Cochrane Library. Search criteria were created by a librarian. Articles published between 1985 and 2016, after the publication date of a large review in 1985, were analyzed independently by 2 neurologists to identify family history rates and pedigrees. Pedigrees were analyzed by a genetic counselor. FINDINGS A total of 1995 studies were found (1988 through the search criteria and 7 through other means). Forty articles met inclusion criteria: 22 large cohort studies, 1 twin-based study, and 17 case reports or small case series. Across the 22 large cohort studies, the positive family history rate of cluster headache varied between 0% and 22%, with a median of 8.2%. The largest 5 studies, of 1134, 785, 693, 609, and 500 probands each, had a positive family history in 18.0% (numerator not provided), 5.1% (40 of 785 cases), 10.0% (numerator not provided), 2.0% (12 of 609 cases), and 11.2% (56 of 500 cases), respectively. No meta-analysis was performed, given differences in methodologies. Separately, 1 twin-based study examined 37 twin pairs and reported a concordance rate of 5.4% (2 pairs). Finally, 67 pedigrees were identified. Most pedigrees (46 of 67 [69%]) were consistent with an autosomal dominant pattern, but 19 of 67 (28%) were consistent with an autosomal recessive inheritance pattern; 10 pedigrees of probable or atypical cluster headache were identified, and all were consistent with an autosomal dominant inheritance pattern. The sex ratio for cluster headache in identified pedigrees was 1.39 (103:74) in affected men and boys compared with affected women and girls, which is lower than that of the general cluster headache population. CONCLUSIONS AND RELEVANCECluster headache is an inherited disorder in a subset of families and is associated with multiple hereditary patterns. There is an unexpectedly high preponderance of women and girls with familial cluster headache; genetic subanalyses limited to female participants are necessary to further explore this observation, because these data are otherwise masked by the higher numbers of male participants with cluster headache. Overall, this systematic review supports the notion that familial cluster headache is likely the result of multiple susceptibility genes as well as environmental factors.

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Combined genotype of HCRTR2 and CLOCK variants in a large family of cluster headache with familial periodicity phenotype

Popescu¹

2023

J Neurol

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Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population

Cited by 11 publications

References 54 publications

No Association Between G1246A Polymorphism in HCRTR2 Gene and Risk of Cluster Headache: Evidence From an Updated Meta-Analysis of Observational Studies

No Association Between G1246A Polymorphism in HCRTR2 Gene and Risk of Cluster Headache: Evidence From an Updated Meta-Analysis of Observational Studies

Family History of Cluster Headache

Combined genotype of HCRTR2 and CLOCK variants in a large family of cluster headache with familial periodicity phenotype

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