偏头痛伴先兆 8q22.1 变异的基因型-表型分析。

A genotype-phenotype analysis of the 8q22.1 variant in migraine with aura.

机构信息

The Danish Headache Center, Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.

出版信息

Eur J Neurol. 2012 Apr;19(4):603-9. doi: 10.1111/j.1468-1331.2011.03588.x. Epub 2011 Nov 22.

Abstract

BACKGROUND AND PURPOSE

Although the genetics of familial hemiplegic migraine are being unraveled, this is not the case for the prevalent types of migraine. However, a recent genome wide association study (GWAS) reported an association of the single nucleotide polymorphism (SNP) rs1835740 and migraine. The aim of this study is to evaluate the association of clinical characteristics in migraine with aura (MA) with the newly discovered minor allele A of rs1835740 at 8q22.1.

METHODS

Participants were recruited from the Danish Headache Center and from specialist practices during the periods 1999-2002 and 2005-2006, and diagnosed according to the International Classification of Headache Disorders (ICHD-II) using a validated physician-conducted semi-structured interview. A large number of clinical characteristics were systematically determined. Caucasians of Danish ancestry diagnosed with MA and successfully genotyped for the SNP rs1835740 were included. Patients with hemiplegic migraine were excluded. Blood samples were collected for extraction of genomic DNA and genotyped for the common susceptibility variant rs1835740.

RESULTS

Six hundred and ninety one successfully genotyped MA patients with substantial description of their clinical characteristics were included. Two hundred and fifty one were heterozygous and 40 were homozygote for the variant marker. Carriers of the rs1835740 variant showed a non-significant tendency towards having a higher frequency of aura symptoms and a non-significant tendency towards milder migraine headache characteristics and fewer accompanying symptoms. These tendencies were not increased in homozygote carriers.

CONCLUSION

None of the clinical characteristics of MA were significantly influenced by the common susceptibility variant on 8q22.1.

摘要

背景与目的

尽管家族性偏瘫性偏头痛的遗传学正在被揭示,但常见偏头痛类型则并非如此。然而,最近的一项全基因组关联研究(GWAS)报告了单核苷酸多态性(SNP)rs1835740 与偏头痛之间的关联。本研究旨在评估新发现的 8q22.1 上的 SNP rs1835740 的次要等位基因 A 与偏头痛伴先兆(MA)的临床特征之间的关联。

方法

参与者是在 1999-2002 年和 2005-2006 年期间从丹麦头痛中心和专科诊所招募的,并根据国际头痛疾病分类(ICHD-II)使用经过验证的医师进行的半结构化访谈进行诊断。系统地确定了大量的临床特征。包括成功对 SNP rs1835740 进行基因分型且诊断为 MA 的白种人丹麦血统患者,并排除了偏瘫性偏头痛患者。采集血样提取基因组 DNA 并对常见的易感变异 rs1835740 进行基因分型。

结果

共纳入 691 例成功进行基因分型的 MA 患者,他们的临床特征得到了充分描述。251 例为杂合子,40 例为纯合子。携带 rs1835740 变异的个体显示出出现先兆症状的频率更高的非显著趋势,偏头痛头痛特征更轻且伴随症状更少的非显著趋势。但这些趋势在纯合子携带者中并未增加。

结论

8q22.1 上常见的易感变异并未显著影响 MA 的任何临床特征。

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