Sir H. N. Medical Research Society, Sir H. N. Hospital & Research Centre, Mumbai, India.
Department of Molecular Medicine, Reliance Life Sciences Pvt. Ltd., Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, India.
Indian J Med Res. 2017 Oct;146(4):505-513. doi: 10.4103/ijmr.IJMR_1500_15.
BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is a major health concern in India. The aim of the study was to identify single nucleotide polymorphisms (SNPs) associated with AMI in patients using dedicated chip and validating the identified SNPs on custom-designed chips using high-throughput microarray analysis.
In pilot phase, 48 AMI patients and 48 healthy controls were screened for SNPs using human CVD55K BeadChip with 48,472 SNP probes on Illumina high-throughput microarray platform. The identified SNPs were validated by genotyping additional 160 patients and 179 controls using custom-made Illumina VeraCode GoldenGate Genotyping Assay. Analysis was carried out using PLINK software.
From the pilot phase, 98 SNPs present on 94 genes were identified with increased risk of AMI (odds ratio of 1.84-8.85, P=0.04861-0.003337). Five of these SNPs demonstrated association with AMI in the validation phase (P=0.05). Among these, one SNP rs9978223 on interferon gamma receptor 2 [IFNGR2, interferon (IFN)-gamma transducer 1] gene showed a significant association (P=0.00021) with AMI below Bonferroni corrected P value (P=0.00061). IFNGR2 is the second subunit of the receptor for IFN-gamma, an important cytokine in inflammatory reactions.
INTERPRETATION & CONCLUSIONS: The study identified an SNP rs9978223 on IFNGR2 gene, associated with increased risk in AMI patient from India.
急性心肌梗死（AMI）是印度的一个主要健康关注点。本研究的目的是使用专用芯片鉴定与 AMI 相关的单核苷酸多态性（SNP），并使用高通量微阵列分析在定制设计的芯片上验证鉴定的 SNP。
在试点阶段，使用 Illumina 高通量微阵列平台上的 48,472 个 SNP 探针的人类 CVD55K BeadChip 对 48 例 AMI 患者和 48 例健康对照者进行 SNP 筛查。使用定制的 Illumina VeraCode GoldenGate 基因分型检测对另外 160 例患者和 179 例对照者进行鉴定的 SNP 进行验证。使用 PLINK 软件进行分析。
从试点阶段开始，在 94 个基因中鉴定出 98 个 SNP，这些 SNP 增加了 AMI 的风险（比值比为 1.84-8.85，P=0.04861-0.003337）。在验证阶段，其中 5 个 SNP 与 AMI 相关（P=0.05）。在这些 SNP 中，干扰素 γ受体 2 [IFNGR2，干扰素（IFN）-γ转导器 1]基因上的 SNP rs9978223 与 AMI 显著相关（P=0.00021），且未经过 Bonferroni 校正的 P 值（P=0.00061）。IFNGR2 是 IFN-γ受体的第二个亚基，IFN-γ 是炎症反应中一种重要的细胞因子。
本研究鉴定出印度 AMI 患者 IFNGR2 基因上的 SNP rs9978223，与 AMI 风险增加相关。
