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基于孟德尔随机化的脂代谢特征与偏头痛风险的相关性研究。

Mendelian randomization study of lipid metabolism characteristics and migraine risk.

机构信息

Department of Neurology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, People's Republic of China.

West China-PUMC C.C. Chen Institute of Health, Sichuan University, Chengdu, People's Republic of China.

出版信息

Eur J Pain. 2024 Jul;28(6):978-986. doi: 10.1002/ejp.2235. Epub 2024 Jan 6.

Abstract

BACKGROUND

The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk.

METHODS

Single-nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid-lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome-wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid-lowering drugs with migraine risk.

RESULTS

Regarding serum lipids, it was found that SNPs related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL-C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL-C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL-C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000).

CONCLUSIONS

There is a relationship between lipid metabolism characteristics and migraine risk.

SIGNIFICANCE

Based on the genome-wide association summary data, single-nucleotide polymorphisms (SNPs) related to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL-C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL-C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development.

摘要

背景

血清脂质与偏头痛之间的关联存在争议。然而,随机对照试验表明,他汀类药物可能对偏头痛的预防有效。在这项研究中,我们旨在研究脂质代谢与偏头痛风险之间的关系。

方法

从全基因组关联研究(GWAS)汇总数据中提取与血清脂质特征相关的单核苷酸多态性(SNP),以及针对 APOB、CETP、HMGCR、NPC1L1 和 PCSK9 的降脂药物的作用。GWAS 汇总数据分别来自全球脂质遗传联盟(GLGC)、英国生物库和芬兰基因研究。采用孟德尔随机化(MR)分析评估血清脂质特征与降脂药物与偏头痛风险之间的关联。

结果

关于血清脂质,研究发现与高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、非高密度脂蛋白胆固醇(非 HDL-C)、总胆固醇(TC)或甘油三酯(TG)水平相关的 SNP 与偏头痛、有先兆偏头痛(MA)或无先兆偏头痛(MO)无关。此外,与较高 LDL-C 水平相关的 HMGCR 基因型与偏头痛(OR=1.46,p=0.035)和 MA(OR=2.03,p=0.008)风险增加相关;然而,与较高 LDL-C 水平相关的 PCSK9 基因型与偏头痛(OR=0.75,p=0.001)和 MA(OR=0.69,p=0.004)风险降低相关;与较高 LDL-C 水平相关的 APOB 基因型与 MO(OR=0.62,p=0.000)风险降低相关。

结论

脂质代谢特征与偏头痛风险之间存在关联。

意义

基于全基因组关联汇总数据,与高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、非高密度脂蛋白胆固醇(非 HDL-C)、总胆固醇(TC)或甘油三酯(TG)水平相关的单核苷酸多态性(SNP)与偏头痛、有先兆偏头痛(MA)或无先兆偏头痛(MO)的风险无关。然而,与较高 LDL-C 水平相关的 HMGCR 基因型显示出偏头痛和 MA 的风险增加。与较高 LDL-C 水平相关的 APOB 或 PCSK9 基因型显示出 MO 或偏头痛和 MA 的风险降低。这些结果表明,脂质代谢特征与偏头痛发展风险之间可能存在关系。

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