Vitamin D receptor and binding protein genes variants in patients with migraine.

BACKGROUND/OBJECTIVES: Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25-hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single-nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case-control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. METHODS: We genotyped 290 patients diagnosed with migraine and 300 age-matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. RESULTS: We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). CONCLUSIONS: In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies.

Lack of Association between Common LAG3/CD4 Variants and Risk of Migraine.

Several papers have been published suggesting a probable role of inflammatory factors in the etiopathogenesis of migraine. In this study, we investigated the possible association between common variants in the LAG3/CD4 genes (both genes, which are closely related, encode proteins involved in inflammatory and autoimmune responses) in the risk of migraine in a cohort of Caucasian Spanish participants. For this purpose, the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants, using a specific TaqMan-based qPCR assay, were assessed in 290 patients diagnosed with migraine and in 300 healthy controls. The relationship of these variables with several clinical features of migraine was also analyzed. The frequencies of the analyzed LAG3/CD4 genotypes did not differ significantly between the two study groups and were not related to the sex, age at onset of migraine, family history of migraine, presence or absence of aura, or the triggering effect of ethanol on migraine episodes. These results suggest a lack of association between common variants in the LAG3/CD4 genes and the risk of developing migraine in the Caucasian Spanish population.

An Update on the Epidemiology of Uveitis in an Urban Setting in Northern Madrid, Spain.

PURPOSE: To describe the incidence, prevalence and etiologies of uveitis in Madrid, Spain. METHODS: A retrospective cross-sectional study was performed in a single hospital. All consecutive cases of uveitis that attended the Hospital during year 2019 were included. Mean incidence and prevalence were calculated. RESULTS: Three hundred and one cases were included. Of these, 127 were incident. This represents an incidence of 21.24 new cases per 100,000 persons/year, and a prevalence was 50.43 cases per 100,000 persons. Mean age was 56.89 ± 18.78 years, and 159 were women (52.8%). Sixty-two cases were infectious (20.6%). Age (p = .005), initial visual acuity (p = .001) and cystoid macular oedema (CMO; p = .010) were found to be independent predictors of the final best corrected visual acuity (BCVA) in patients with uveitis. CONCLUSIONS: Uveitis affects approximately 1 in 1800 persons in northern Madrid. Younger age, better initial visual acuities and the presence of CMO predicted better final BCVA.

Increased serum diamine oxidase activity in nonallergic patients with migraine.

BACKGROUND/OBJECTIVES: Histamine has shown a possible role in the etiopathogenesis of migraine. It has been reported an association between some polymorphisms in the diamine oxidase (DAO) gene and migraine, especially in women. Two studies addressing DAO activity in migraine patients showed conflicting results. We investigated the possible relationship of serum DAO activity and histamine levels and 3 polymorphisms in the DAO gene with the risk for migraine. METHODS: We studied the frequencies of DAO rs10156191, rs1049742 and rs1049793 genotypes and allelic variants in 298 migraine patients and 360 healthy controls (using a TaqMan-based qPCR assay), and serum DAO activity and histamine levels in a subset of 99 migraine patients and 115 controls with strict exclusion criteria, and analysed the relationship of these variables with several clinical features of migraine. RESULTS: The frequencies of the DAO genotypes and allelic variants analysed were similar in migraine patients and controls. Serum DAO activity was significantly higher in migraine patients (Vmax/Km 4.24 ± 2.93 vs. 3.60 ± 7.64, p < 0.001), especially in females (Vmax/Km 4.63 ± 2.96 vs. 3.18 ± 2.32, p < 0.0001), while serum histamine was similar in both study groups. CONCLUSION: Serum DAO activity was increased in patients with migraine, especially in females, while serum histamine levels were normal. None of the studied polymorphisms was associated with the risk for migraine.

Association between endothelial nitric oxide synthase (NOS3) rs2070744 and the risk for migraine.

Because nitric oxide could play an important role in the pathogenesis of migraine (suggested by experimental, neuropathological, biochemical, and pharmacological data), and a recent meta-analysis showed an association between the single-nucleotide polymorphism (SNP) rs2070744 in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) and the risk for migraine in Caucasians, we attempted to replicate the possible association between this SNP and the and the risk for migraine in the Caucasian Spanish population. The frequencies for the NOS3 rs2070744 genotypes and allelic variants were assessed in 283 migraine patients and 287 healthy controls with a TaqMan-based qPCR Assay. The putative influence on genotype frequency of age at onset of migraine attacks, gender, family history of migraine, absence or presence of aura, and triggering of migraine attacks by ethanol, were also analyzed. The frequencies of NOS3 rs2070744 genotypes and allelic variants were not associated with the risk for migraine (OR [95%] CI for the minor allele = 0.91 [0.72-1.15]) and were not influenced by age at onset of migraine, gender, presence of aura, or triggering of migraine attacks by ethanol. NOS3 rs2070744CC genotypes were significantly more frequent in patients with a family history of migraine. NOS3 rs2070744 SNP is not associated with the risk for migraine in Caucasian Spanish people although it might be related to family history.

Gamma-aminobutyric acid (GABA) receptors GABRA4, GABRE, and GABRQ gene polymorphisms and risk for migraine.

Several biochemical, pharmacological, neurophysiological and experimental data suggest a possible role of gamma-aminobutyric acid (GABA) in the pathogenesis of migraine. We investigated the possible association of the most common single nucleotide polymorphisms (SNPs) in the GABA receptor alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) genes with the risk for migraine. A TaqMan-based qPCR assay designed to detect the most common SNPs in the GABRA4 (rs2229940), GABRE (rs1139916), and GABRQ (rs3810651) was performed in 197 migraine patients and 394 age- and gender-matched controls. The possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes was also studied. The frequency of GABRE rs1139916AA genotype was significantly lower in the migraine group only in the female gender, but the differences did not reach statistical significance after correction for multiple comparisons. The mean ± SD age at onset of migraine was significantly lower in patients with GABRQ rs3810651AA as compared with the other two genotypes. Positive family history of migraine and presence or absence of aura did not influence the frequencies of the genotypes of the three SNPs studied. Triggering of migraine by ethanol was significantly less frequent in patients with GABRA4 rs2229940GG and more frequent in patients with GABRQ 3810651TT genotype, but the differences lost statistical significance after correction for multiple comparisons. GABRQ rs3810651 could play a role in the modification of age at onset of migraine.

Gamma-Aminobutyric Acid (Gaba) Receptors Rho (Gabrr) Gene Polymorphisms and Risk for Migraine.

BACKGROUND/OBJECTIVES: The possible role of gammaaminobutyric acid (GABA) in the pathogenesis of migraine has been suggested by a number of biochemical, pharmacological, neurophysiological and experimental data. We investigated the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptor rho1, 2, and 3 genes (GABRR1, GABRR2, and GABRR3) and the risk of developing migraine. METHODS: The frequency of GABRR1 rs12200969, GABRR1 rs1186902, GABRR2 rs282129, and GABRR3 rs832032 genotypes and allelic variants were studied in a case-control association study involving 197 patients with migraine and 278 healthy controls by means of a TaqMan-based qPCR Assay. We also studied the possible influence of gender, age at onset of migraine, positive family history of migraine, presence or absence of aura, and triggering of migraine by ethanol on the frequency of the genotypes. RESULTS: The frequencies of the genotypes and allelic variants of the 4 SNPs were similar in migraine patients and controls. Gender, positive family history of migraine, presence or absence of aura, and triggering of migraine attacks by ethanol did not influence the frequency of these genotypes. Carriers of the minor allele of the rs1186902 SNP showed a trend towards later onset of migraine. CONCLUSION: The most common polymorphisms in the GABRR genes seemed to be not associated with the risk for migraine in Caucasian Spanish people, although one of them (GABRR1 rs1186902) shows a statistically significant association with the age of onset of migraine.

Neuronal Nitric Oxide Synthase (nNOS, NOS1) rs693534 and rs7977109 Variants and Risk for Migraine.

BACKGROUND/OBJECTIVES: Many biochemical, pharmacological, neuropathological, and experimental data suggest a possible role of nitric oxide in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the neuronal nitric oxide synthase gene (NOS1 or nNOS; chromosome 12q24.22) and the risk for migraine. METHODS: We studied the frequency of the of rs7977109 and rs693534 genotypes and allelic variants in 197 patients with migraine and 308 healthy controls using a TaqMan-based qPCR assay. As a secondary analysis, we studied the possible influence of gender, age at onset of migraine, positive family history of migraine, and presence or absence of aura on the genotypes frequency. RESULTS: The frequencies of rs7977109 and rs693534 genotypes and allelic variants were not associated with the risk for migraine with OR for minor alleles = 0.94 (95% CI 0.72-1.23) and = 0.88 (0.68-1.15), respectively, and the lack of association was not influenced by gender, age at onset of migraine, positive family history of migraine, and presence or absence of aura. CONCLUSION: NOS1 rs7977109 and rs693534 genotypes and allelic variants are not associated with the risk for migraine in Caucasian Spanish people.

Diamine oxidase†rs10156191 and rs2052129 variants are associated with the risk for migraine.

BACKGROUND: Histamine has been implicated in the pathogenesis of migraine. We investigated the possible association between functional single nucleotide polymorphisms (SNPs) in the diamine oxidase gene (DAO; chromosome 7q36.1, involved in histamine metabolism) and the risk for migraine. METHODS: We studied the frequency of the rs2052129, rs10156191, rs1049742, and rs1049793 genotypes and allelic variants in 197 patients with migraine and 245 healthy controls using a TaqMan-based qPCR Assay. RESULTS: The DAO SNP rs10156191, which is related to decreased DAO enzyme activity, is associated with the risk of developing migraine, particularly in women. The odds ratio (OR) for the defect allele positivity is 1.61 (95% confidence interval 1.31-2.37) for overall migraine patients and 2.08 (1.29-3.36) for women suffering from migraine. The association was not influenced by confounders such as the age at onset, the presence of aura, positivity of alcohol as a triggering factor, positive family history of aura, or family history of allergy. Multiple regression analyses did not confirm association with the rest of genetic factors. CONCLUSION: Our findings, which should be framed as hypothesis generating, suggest that DAO genotypes and allelic variants are associated with the risk for migraine in Caucasian Spanish people, especially in women.

SLC1A2 rs3794087 variant and risk for migraine.

BACKGROUND/OBJECTIVES: Glutamate has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism rs3794087 in the SLC1A2 gene (EATT2 or GLT-1; chromosome 11p13-p12 involved in glutamate transport) and the risk for migraine and for triggering migraine attacks by alcohol. METHODS: We studied the frequency of the rs3794087 genotypes and allelic variants in 197 patients with migraine and 308 healthy controls using a TaqMan-based qPCR assay. RESULTS: The frequencies of the rs3794087 genotypes and alleles were similar in patients with migraine and controls, and were unrelated with the age of onset of migraine, gender, presence or absence of aura, or family history of migraine CONCLUSION: rs3794087 genotype and allelic variants were not related with the risk for migraine in Caucasian Spanish people.

Paraoxonase 1 (PON1) polymorphisms and risk for migraine.

The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by the gene PON1 (chromosome 7q21.3) plays a role as an antioxidant molecule through several mechanisms. Because oxidative stress has been implicated in the pathogenesis of migraine, we have investigated the possible association between the nonsynonymous polymorphisms 55LM and 192QR in the PON1 and the risk for migraine. We studied the frequency of the PON1 genotypes and allelic variants in 197 patients with migraine and 220 healthy controls using a TaqMan single nucleotide polymorphism analysis. The frequencies of the PON1 genotypes and PON1 allelic variants did not differ significantly between patients with migraine and controls, and were unrelated with gender, family history of migraine, and presence or absence of aura. The frequencies of the genotype PON1 192QQ and the allelic variant PON1 192Q were significantly higher in patients with earlier onset of migraine. The results of the present study suggest that PON1 polymorphisms are not related with the risk for migraine in Caucasian Spanish people, although PON1 192Q/Q genotype and PON1 192Q allelic variant should be related with an earlier onset of migraine.

Alcohol dehydrogenase 2 genotype and risk for migraine.

BACKGROUND/OBJECTIVES: Alcohol has been traditionally considered a possible migraine trigger factor. Alcohol-dehydrogenase (ADH) enzymes are thought to play important roles in the metabolism of ethanol. Relevant polymorphism has been found only for 2 of the ADH genes (mapped on chromosome ): ADH 1B, betapolypeptide (ADH2) and ADH3. The polymorphism rs1229984, located in the third exon of the human ADH2 gene, causes the amino acid substitution Arg48His. The aim of this study was to investigate the possible association between ADH2 polymorphism and the risk for migraine and for triggering migraine attacks. METHODS: We studied the frequency of the ADH2 genotypes and allelic variants in 197 patients with migraine and 255 healthy controls using allele-specific PCR amplification and MslI-RFLP's analyses. RESULTS: The frequencies of ADH2 Arg/His genotype and of ADH2 His allele were significantly lower in patients with migraine when compared with those of controls, and were unrelated with the age of onset of migraine attacks, family history of migraine or presence of aura. The frequency of the allelic variant ADH2 His (ADH2*2) was significantly higher in the group of patients who reported triggering of migraine by alcohol when compared with the group who reported no effect. CONCLUSION: The results of the present study suggest that ADH2 Arg/His genotype should be associated with a decreased risk for migraine, while the ADH2 His allelic variant should be related with the risk for triggering migraine attacks after alcohol consumption in our population of migraine patients.

Histamine-N-methyl transferase polymorphism and risk for migraine.

BACKGROUND/OBJECTIVES: Histamine has been implicated in the pathogenesis of migraine. In the CNS, histamine is almost exclusively metabolized by the polymorphic enzyme histamine N-methyltransferase (HNMT). The HNMT gene (chromosome 2q22.1), shows diverse single nucleotide polymorphisms. One of these, located in exon 4 C314T, causes the amino acid substitution Thr105Ile, related to decreased enzyme activity. The aim of this study was to investigate the possible association between HNMT polymorphism and the risk for migraine. METHODS: We studied the frequency of the HNMT genotypes and allelic variantes in 197 patients with migraine and 245 healthy controls using a PCR-RLFP method. RESULTS: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between migraine patients and controls, and were unrelated with the age of onset of migraine attacks, gender, personal history of allergic diseases, family history of migraine, or presence of aura. CONCLUSION: The results of the present study suggest that HNMT polymorphism in not related with the risk for migraine.