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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 ( NOS 1 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 T aq M an-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 NOS 1 rs7977109 and rs693534 genotypes and allelic variants are not associated with the risk for migraine in Caucasian Spanish people. [ABSTRACT FROM AUTHOR]

The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support, many research groups, composed of basic and clinical researchers, have been actively working for decades in this field. Their contributions made an international impact and paved the way for further studies and pharmacogenomics implementation in clinical practice. In this manuscript, that makes part of the Special Issue entitled Spanish Pharmacology, we present an analysis of the state of the art of Pharmacogenetics and Pharmacogenomics research in Europe, we compare it with the developments in Spain, and we summarize the most salient contributions since 1988 to the present, as well as recent developments in the clinical application of pharmacogenomics knowledge. Finally, we present some considerations on how we could improve translation to clinical practice in this specific scenario. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Background/objectives: Recently, a genome-wide association study revealed a significant statistical association between LINGO1 rs9652490 and rs11856808 polymorphisms and the risk of developing essential tremor (ET) in Icelandic people. Because the results of further association studies were controversial, we conducted a meta-analysis including all the studies published on the risk of ET related with these polymorphisms. Methods: The metaanalysis included 11 association studies between LINGO1 rs9652490 (3972 ET patients, 20,714 controls) and 7 association studies between LINGO1 rs11856808, and risk for ET (2076 ET patients, 18,792 controls), and was carried out by using the software Meta-Disc 1.1.1 (http://www.hrc.es/investigacion/metadisc.html; Unit of Clinical Statistics, Hospital Ramón y Cajal, Madrid, Spain). Heterogeneity between studies in terms of degree of association was tested using the Q-statistic. Results: Global diagnostic odds-ratios (ORs) and 95% confidence intervals (CI) for rs9652490 and rs11856808 of the total series were, respectively, 1.17 (1.00–1.36) (p=0.069) and 1.20 (1.05–1.36) (p=0.016). After excluding data on Icelandic people of the discovery series (that was responsible of a high degree of heterogeneity for rs9652490 polymorphism), the ORs and CI were 1.10 (0.97–1.26) (p=0.063) and 1.12 (0.99–1.27) (p=0.034). Global ORs and 95% CI for rs9652490 and rs11856808 of familial ET patients were, respectively, 1.27 (1.03–1.57) (p=0.014) and 1.21 (1.10–1.44) (p=0.031). Conclusions: The results of the meta-analysis suggest a relationship between LINGO1 rs11856808 polymorphism and the risk for ET and for familial ET, while rs9652490 polymorphism was only related with the risk for familial ET. [Copyright &y& Elsevier]