EHMTI-0047. Genetic association and gene expression studies suggest that genetic variants in the SYNE1 and TNF genes are related to menstrual migraine
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ABSTRACT:
SUBMITTER: Griffiths L
PROVIDER: S-EPMC4181291 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundMenstrual migraine (MM) encompasses pure menstrual migraine (PMM) and menstrually-related migraine (MRM). This study was aimed at investigating genetic variants that are potentially related to MM, specifically undertaking genotyping and mRNA expression analysis of the ESR1, PGR, SYNE1 and TNF genes in MM cases and non-migraine controls.MethodsA total of 37 variants distributed across 14 genes were genotyped in 437 DNA samples (282 cases and 155 controls). In addition levels of gene expression were determined in 74 cDNA samples (41 cases and 33 controls). Association and correlation analysis were performed using Plink and RStudio.ResultsSNPs rs3093664 and rs9371601 in TNF and SYNE1 genes respectively, were significantly associated with migraine in the MM population (p = 0.008; p = 0.009 respectively). Analysis of qPCR results found no significant difference in levels of gene expression between cases and controls. However, we found a significant correlation between the expression of ESR1 and SYNE1, ESR1 and PGR and TNF and SYNE1 in samples taken during the follicular phase of the menstrual cycle.ConclusionsOur results show that SNPs rs9371601 and rs3093664 in the SYNE1 and TNF genes respectively, are associated with MM. The present study also provides strong evidence to support the correlation of ESR1, PGR, SYNE1 and TNF gene expression in MM.
| S-EPMC4196204 | biostudies-literature
Project description:BackgroundIn 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. While sub-type analysis for migraine without aura (MO) and migraine with aura (MA) found some loci showed specificity to MO, the study did not test the loci with respect to other subtypes of migraine. This study aimed to test the hypothesis that single nucleotide polymorphisms (SNPs) robustly associated with migraine are individually or collectively associated with menstrual migraine (MM).MethodsGenotyping of migraine susceptibility SNPs was conducted using the Agena MassARRAY platform on DNA samples from 235 women diagnosed with menstrual migraine as per International Classification for Headache Disorders II (ICHD-II) criteria and 140 controls. Alternative genotyping methods including restriction fragment length polymorphism, pyrosequencing and Sanger sequencing were used for validation. Statistical analysis was performed using PLINK and SPSS.ResultsGenotypes of 34 SNPs were obtained and investigated for their potential association with menstrual migraine. Of these SNPs, rs2506142 located near the neuropilin 1 gene (NRP1), was found to be significantly associated with menstrual migraine (p = 0.003). Genomic risk scores were calculated for all 34 SNPs as well as a subset of 7 SNPs that were nearing individual significance. Overall, this analysis suggested these SNPs to be weakly predictive of MM, but of no prognostic or diagnostic value.ConclusionsOur results suggest that NRP1 may be important in the etiology of MM. It also suggests some genetic commonality between common migraine subtypes (MA and MO) and MM. The identification of associated SNPs may be the starting point to a better understanding of how genetic factors may contribute to the menstrual migraine sub-type.
| S-EPMC5906416 | biostudies-literature
Project description:Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17-4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.
| S-EPMC7924177 | biostudies-literature
Project description:Background and aimMigraine is the most common neurological disorder, affecting approximately 12 % of the adult population worldwide, caused by both environmental and genetic factors. Three causative genes have been identified in familial hemiplegic migraine (FHM) families: CACNA1A, ATP1A2, and SCNA1A. Recently, several mutations in KCNK18 have also been found as causative factors in migraine development. The aim of our study was to identify the genetic background of migraine in the Polish population.Material and methodsSixty patients with migraine without aura (MO) or with different types of migraine with aura (MA), including sporadic hemiplegic, familial hemiplegic, and probable familial hemiplegic, were screened for mutations in the four genes previously linked with different types of migraine (ATP1A2, CACNA1A, SCN1A, and KCNK18).ResultsTwo missense mutations were found. One novel mutation in SCN1A, encoding α subunit of sodium channel, causing amino acid change M1500V localized to a region encoding inactivation loop between transmembrane domains III and IV of the channel, was detected in a female FHM patient. The M1500V mutation was absent in a group of 62 controls, as well as in the ExAC database. The second, already known missense mutation S231P in KCNK18 was found in a female MA patient. Additionally, a novel intronic polymorphism possibly affecting alternative splicing of SCN1A, at chr2:16685249, g.77659T>C, and c.4581+32A>G, located between exons 24 and 25, in a region encoding the inactivation loop of the sodium channel was found in a female MO patient. No mutations in ATP1A2 or CACNA1A were found in the study group.ConclusionsThe presence of SCN1A mutations and absence of mutations in ATP1A2 or CACNA1A suggest that the Polish patients represent FHM type 3. On the other hand, the presence of KCNK18 mutation indicated another FHM subtype. It could be speculated that contrary to other European populations, the genetic basis of migraine in the Polish population involves mutations in genes not included in the study. Next-generation sequencing methods should be implemented to identify other migraine-associated variants.
| S-EPMC4706665 | biostudies-literature
Project description:Adolescent idiopathic scoliosis (AIS) is an unexplained and common spinal deformity seen in otherwise healthy children. Its pathophysiology is poorly understood despite intensive investigation. Although genetic underpinnings are clear, replicated susceptibility loci that could provide insight into etiology have not been forthcoming. To address these issues, we performed genome-wide association studies (GWAS) of ?327 000 single nucleotide polymorphisms (SNPs) in 419 AIS families. We found strongest evidence of association with chromosome 3p26.3 SNPs in the proximity of the CHL1 gene (P < 8 × 10(-8) for rs1400180). We genotyped additional chromosome 3p26.3 SNPs and tested replication in two follow-up case-control cohorts, obtaining strongest results when all three cohorts were combined (rs10510181 odds ratio = 1.49, 95% confidence interval = 1.29-1.73, P = 2.58 × 10(-8)), but these were not confirmed in a separate GWAS. CHL1 is of interest, as it encodes an axon guidance protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3. We additionally found AIS associations with loci in CNTNAP2, supporting a previous study linking this gene with AIS. Cntnap2 is also of functional interest, as it interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Our results suggest the relevance of axon guidance pathways in AIS susceptibility, although these findings require further study, particularly given the apparent genetic heterogeneity in this disease.
| S-EPMC3049353 | biostudies-literature
Project description:Hereditary ataxias are classified by inheritance patterns into autosomal dominant, autosomal recessive, X-linked, and mitochondrial modes of inheritance. A large group of adult hereditary ataxias have autosomal dominant inheritance, and autosomal recessive cerebellar ataxias (ARCAs) are rare, with greater diversity in phenotypic and genotypic features. Therefore, comprehensive genetic testing is useful for identifying the genes responsible for ARCAs. We identified two novel pathogenic variants of the SQSTM1 and SYNE1 genes via whole-exome sequencing in patients with ARCAs.
| S-EPMC11364807 | biostudies-literature
Project description:Perimenopause is linked to increased migraine (Mg), especially menstrual Mg (MMg), influenced by hormonal changes. Compared to nonmenstrual attacks, menstrual attacks are more disabling and less responsive to treatment. Women with perimenstrual estrogen withdrawal have been linked to Mg during menstruation, whereas Mg during perimenopause has been linked to unpredictable fluctuations in estrogen levels. It has been widely established that female sex hormones play a role in Mg, but how it occurs remains unclear. This narrative review was identified using Medline and PubMed searches between 1946 and 2021. Search terms included "headache," "migraine," "menstrual migraine," "menstruation," "menopause," "perimenopause," "estrogen," and "progesterone." This article focuses on the candidate genes and female hormones that play a role in MMg. More study is necessary to understand better the environmental components that play a critical role in disease development. Currently, there is insufficient clinical evidence to support the function of menstrual Mg. The specific research facts examined MMg unique candidate genes and female hormonal factors that support their association and found MMg etiologic processes for generating an early diagnostic marker.
| S-EPMC9350771 | biostudies-literature
Project description:Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.
| S-EPMC7907521 | biostudies-literature
Project description:Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing.
| S-EPMC3865589 | biostudies-literature
Project description:ObjectiveTo investigate the association of migraine genetic variants with cerebral blood flow (CBF).BackgroundMigraine is a common disorder with many genetic and non-genetic factors affecting its occurrence. The exact pathophysiological mechanisms underlying the disease remain unclear, but are known to involve hemodynamic and vascular disruptions. Recent genome-wide association studies have identified 44 genetic variants in 38 genetic loci that affect the risk of migraine, which provide the opportunity to further disentangle these mechanisms.MethodsWe included 4665 participants of the population-based Rotterdam Study (mean age 65.0 ± 10.9 years, 55.6% women). Cross-sectional area (mm2 ), flow velocity (mm/s), and blood flow (mL/min) were measured in both carotids and the basilar artery using 2-dimensional phase-contrast magnetic resonance imaging. We analyzed 43 previously identified migraine variants separately and calculated a genetic risk score (GRS). To assess the association with CBF, we used linear regression models adjusted for age, sex, and total brain volume. Hierarchical clustering was performed based on the associations with CBF measures and tissue enrichment.ResultsThe rs67338227 risk allele was associated with higher flow velocity and smaller cross-sectional area in the carotids (Pminimum = 3.7 × 10-8 ). Other variants were related to CBF with opposite directions of effect, but not significantly after multiple testing adjustments (P < 1.4 × 10-4 ). The migraine GRS was not associated with CBF after multiple testing corrections. Migraine risk variants were found to be enriched for flow in the basilar artery (λ = 2.39).ConclusionsThese findings show that genetic migraine risk is complexly associated with alterations in cerebral hemodynamics.
| S-EPMC7003871 | biostudies-literature