Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to test genetic differences in the clinical response to rizatriptan in patients affected by migraine without aura. These genetic differences could be explained by various genes, the HTR1B, encoding the 5-HT(1) receptor subtype, MAOA gene that encodes the monoamino-oxidase, the main metabolic enzyme of this triptan, SLC6A4 (gene encoding the serotonin transporter) and DRD(2) (gene encoding the D(2) receptor), both involved in the pathogenesis of migraine. Fifty unrelated patients affected by migraine without aura (IHS) were included. Patients were divided into two groups (responders and non-responders) according to clinical response. Thirty-one out of fifty patients responded to rizatriptan. A significant difference among the two groups was observed in both allele (p=0.02) and genotype distribution (p=0.03) of DRD2/NcoI. The significant association with the DRD2/NcoI polymorphism in responders suggested that the DRD2/NcoI C allele may be considered a susceptibility factor heralding a good response to rizatriptan.
J Headache Pain 2007 Jun
PMID:Association study between clinical response to rizatriptan and some candidate genes. 1756 39

The aim of the present observational study was to assess the value of the C825T polymorphism of the beta-3 subunit of G proteins (GNB3) as well as of variants in the SLC6A4 gene (5HTTLPR and STin2 VNTR) and DRD2 gene (TaqI A and NcoI) as predictive markers for consistency in headache response to triptans in migraine patients. Consistent responders to triptans were defined as the migraineurs who experienced a > or =2 point reduction in a 4-point scale intensity of pain from 3 (severe) to 0 (absent) 2h after triptan administration, in at least two attacks out of the three. Genotyping was performed by PCR and PCR-RFLP on genomic DNA extracted from peripheral blood. The impact of clinical and biological variables on consistency status of headache response to triptans was evaluated by using a binary logistic regression model with stepwise selection. Forty-three (33%) of the 130 migraine patients included in the study did not consistently respond to triptan administration. In a binary logistic regression model, STin 2.12/12 genotype (OR=3.363, 95% CI: 1.262-8.966, P=0.005) and non-use of migraine prophylactic medications (OR=2.848, 95% CI: 1.019-7.959, P=0.010) were found as significant factors increasing the odds of achieving inconsistent response to triptans. The analysis of classificatory power of the model showed moderate values of sensitivity (0.56), high specificity (0.87), and an overall prediction correctness (0.77). These results support the role of STin2 VNTR polymorphism of serotonin transporter gene as a relevant genetic factor conferring a higher risk of inconsistent response to triptans in migraine patients.
 ...
PMID:The serotonin transporter gene polymorphism STin2 VNTR confers an increased risk of inconsistent response to triptans in migraine patients. 2048 9

Data on the association between the SLC6A4 STin2 VNTR polymorphism and migraine are conflicting. To perform pooled and meta-analyses, we searched for studies published until September 2009 using electronic databases (MEDLINE, EMBASE, Science Citation Index) and reference lists of studies. Assessment for eligibility and extraction of data was performed by two independent investigators. We extracted allele and genotype frequencies for each study. We then calculated study-specific and pooled odds ratios (OR) and 95% confidence intervals (CI) assuming allele and genotype models. We also calculated pooled ORs and 95% CIs based on study-specific effect estimates for the allele model. We included five studies investigating the association between the STin2 VNTR polymorphism and migraine. Results from the allele model suggested a protective effect against migraine for the STin2.9 and STin2.10 alleles compared to the STin2.12 allele among populations of European descent, which however was not significant. Results from the genotype model indicated a significant approximately 25% reduced risk for migraine among carriers of the 10/12 genotype compared with carriers of the 12/12 genotype among all study populations (OR = 0.76, 95% CI 0.60-0.97) for any migraine, which was more pronounced among populations of European descent (OR = 0.68, 95% CI 0.53-0.87). Results for migraine with and without aura were of similar magnitude, but were not statistically significant. Our results suggest a protective effect of non-STin2.12 alleles compared to STin2.12 alleles, respectively, 10/12 and 10/10 genotypes compared to the 12/12 genotype against migraine among populations of European descent. Associations in non-European populations may differ.
J Headache Pain 2010 Aug
PMID:STin2 VNTR polymorphism in the serotonin transporter gene and migraine: pooled and meta-analyses. 2058 26

Sleep bruxism is a sleep-related movement disorder that can be responsible for various pains and dysfunctions in the orofacial region. The aim of the current case-control association study was to investigate the association of genetic, psychological and behavioral factors with sleep bruxism in a Japanese population. Non-related participants were recruited and divided into either a sleep bruxism group (n = 66) or control group (n = 48) by clinical diagnoses and 3-night masseter electromyographic recordings by means of a portable miniature device. The Epworth Sleepiness Scale, Temperament and Character Inventory, NEO-Five Factor Inventory and custom-made questionnaires that asked about familial aggregation, alcohol intake, caffeine intake, cigarette smoking, past stressful life events, daytime tooth-contacting habit, temporomandibular disorder, daily headache, snoring, apnea/hypopnea symptoms, leg-restlessness symptoms and nocturnal-myoclonus symptoms were administered. In addition, 13 polymorphisms in four genes related to serotonergic neurotransmission (SLC6A4, HTR1A, HTR2A and HTR2C) were genotyped. These factors were compared between case (sleep bruxism) and control groups in order to select potential predictors of sleep-bruxism status. The statistical procedure selected five predictors: Epworth Sleepiness Scale, leg-restlessness symptoms, rs6313 genotypes, rs2770304 genotypes and rs4941573 genotypes. A multivariate stepwise logistic regression analysis between the selected predictors and sleep-bruxism status was then conducted. This analysis revealed that only the C allele carrier of HTR2A single nucleotide polymorphism rs6313 (102C>T) was associated significantly with an increased risk of sleep bruxism (odds ratio = 4.250, 95% confidence interval: 1.599-11.297, P = 0.004).This finding suggests a possible genetic contribution to the etiology of sleep bruxism.
 ...
PMID:Association of genetic, psychological and behavioral factors with sleep bruxism in a Japanese population. 2254 12

Migraine is one of the most common primary headache disorders that affects 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura (MA) and migraine without aura (MO). Both serotonergic and hypocretinergic systems are involved in the migraine pathomechanism. Polymorphisms in the serotonin transporter gene (SLC6A4) and the hypocretin receptor 1 gene (HCRTR1) may be risk factors for migraine development due to their ability to affect serotonin and hypocretin-1 (HCRT-1) concentrations. The aim of the study was to analyze, for the first time in the Polish population, the 5-HT transporter linked polymorphic region (5-HTTLPR) in SLC6A4, G1222A (rs2271933) and the never before studied *G29A (rs41263963) polymorphisms in the HCRTR1 gene, as well as the 5-HT and hypocretin-1 plasma concentrations in migraine patients (MA, MO) and control subjects. The study included 123 patients that were diagnosed with migraine and 123 control subjects. Methods such as PCR, HRMA and sequencing were used for genotyping, while 5-HT was determined by HPLC/EC and hypocretin-1 by ELISA. No significant differences were observed in 5-HTTLPR frequencies. The A allele of HCRTR1 G1222A occurred more often in MO, while the GA genotype of HCRTR1 *G29A was more frequent among MA when compared to control group (p < 0.05). The mean age of migraine onset in individuals with HCRTR1 *G29A was 18 years old for patients with MA and 26 years old for MO patients. The localization and type of HCRTR1 polymorphisms (G1222A-missense variant in exon 7, *G29A-3'UTR variant) may predispose patients to the clinical subtype of migraine: MO or MA, respectively. In control subjects, the short allele of 5-HTTLPR tended to decrease the 5-HT concentration, while the A allele of HCRTR1 G1222A decreased both 5-HT and hypocretin-1 levels. Serotonin concentrations differed in terms of clinical features of migraine. The relation between genotypes of 5-HTTLPR, HCRTR1 G1222A, and 5-HT concentrations may bedisturbed in migraine. It seems that HCRTR1 *G29A is more strongly associated with regulating the 5-HT in patients with MA than MO, and therefore may contribute to the early age of onset for migraine.
 ...
PMID:The New *G29A and G1222A of HCRTR1, 5-HTTLPR of SLC6A4 Polymorphisms and Hypocretin-1, Serotonin Concentrations in Migraine Patients. 2992 28