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rs2651899变异与来自北印度人群的无先兆偏头痛风险相关。

rs2651899 variant is associated with risk for migraine without aura from North Indian population.

作者信息

Kaur Sukhvinder, Ali Arif, Ahmad Uzair, Pandey A K, Singh Balkirat

机构信息

UGC-PDF, 309, Gene Expression Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.

UGC-BSR-FF, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.

出版信息

Mol Biol Rep. 2019 Feb;46(1):1247-1255. doi: 10.1007/s11033-019-04593-1. Epub 2019 Jan 11.

Abstract

Recently a GWAS study had identified 38 genomic variants commonly found in humans that influence migraine risk. For further replicate these findings, we selected two SNPs; rs2651899 on chromosome 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population. In this case-control association study, 300 unrelated subjects, including 150 migraineurs (43 migraine with aura and 107 migraine without aura) and 150 healthy controls were selected to collect genomic DNA. Polymerase chain reaction and restriction-fragment-length polymorphism methods were performed for genotyping of these variants. Univariate and multivariate analyses were done to find the association of different genotypes and alleles of these SNPs with migraine and its subgroups. We found a statistically significant difference in migraineurs with control for PRDM16 rs2651899 polymorphism at genotypic (p < 0.05), allelic (p = 0.022; OR 1.462; 95% CI 1.058-2.022) and for dominant model (p = 0.011; OR 1.957; 95% CI 1.169-3.276). A similar trend was observed both on subgroup and gender analysis in migraine without aura (MO) and females respectively for rs2651899 variant. For the other SNP (rs10166942), statistically non-significant differences were reported in the allelic/genotypic frequencies between migraineurs and controls as p > 0.05. However, on subgroup analysis we found statistically significant differences at genotypic (p < 0.05) and dominant models in migraine with aura (MA) and in males with that of entire controls. But no significant association was found at allelic level in both subgroup and gender analysis for rs10166942. This research study showed that rs2651899 is a potential genetic marker for migraine susceptibility in MO and female subgroup at both genotypic and allelic level in the North Indian population and found that rs10166942 variant may be a potential marker for MA and male subgroup. Further work with large sample size is required for these SNPs to understand their functional mechanisms and to strengthen our results.

摘要

最近一项全基因组关联研究(GWAS)已鉴定出在人类中常见的38种基因组变异,这些变异会影响偏头痛风险。为了进一步重复这些发现,我们选择了两个单核苷酸多态性(SNP);PRDM16基因中位于1号染色体1p36.32上的rs2651899以及靠近TRPM8基因的2号染色体2q37.1上的rs10166942,因为此前在北印度人群中尚未对这些变异与偏头痛的关联进行过大量研究。在这项病例对照关联研究中,选取了300名无亲缘关系的受试者,包括150名偏头痛患者(43名有先兆偏头痛和107名无先兆偏头痛)以及150名健康对照,以收集基因组DNA。采用聚合酶链反应和限制性片段长度多态性方法对这些变异进行基因分型。进行单变量和多变量分析以找出这些SNP的不同基因型和等位基因与偏头痛及其亚组的关联。我们发现,在PRDM16基因的rs2651899多态性方面,偏头痛患者与对照组在基因型(p < 0.05)、等位基因(p = 0.022;优势比1.462;95%置信区间1.058 - 2.022)以及显性模型(p = 0.011;优势比1.957;95%置信区间1.169 - 3.276)上存在统计学显著差异。对于rs2651899变异,在无先兆偏头痛(MO)亚组和女性中的性别分析中也观察到了类似趋势。对于另一个SNP(rs10166942),偏头痛患者与对照组之间的等位基因/基因型频率差异在统计学上无显著意义,因为p > 0.05。然而,在亚组分析中,我们发现在有先兆偏头痛(MA)以及男性与整个对照组相比时,在基因型(p < 0.05)和显性模型上存在统计学显著差异。但在rs10166942的亚组和性别分析中,等位基因水平均未发现显著关联。这项研究表明,在北印度人群中,rs2651899在基因型和等位基因水平上都是MO和女性亚组偏头痛易感性的潜在遗传标记,并且发现rs10166942变异可能是MA和男性亚组的潜在标记。需要对这些SNP进行更大样本量的进一步研究,以了解其功能机制并强化我们的结果。

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