NLRP3 Inflammasome Gene Polymorphisms Variably Associated with its Serum Levels in Acute Myocardial Infarction

Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) plays a pivotal role in initiation of inflammation. genetic variation in NLRP3 gene have been proposed to predispose several inflammatory diseases. This study aimed to evaluate the risk of NLRP3 (exon 3) gene polymorphisms and its relation with serum NLRP3 among myocardial infarction.

Case-control study involved 69 patients with Myocardial Infarction and 53 controls, from each subject 3 mL were collected and used for DNA extraction then the amplified exon 3 genes were sequenced by Sanger method. Serum NLRP3 was quantified using sandwich ELISA.

According to the results Q705K found to possess a 16.21 times risk for MI incidence compared with controls. In addition, 44 novel single nucleotide polymorphisms have been identified at the position 14347, 14261, 14240 and 14229 and their allelic variants as a risk factor for MI incidence as 3.92, 8.6, 2.04 and 4.57 when compared with their relevant allele in controls respectively. Statistically high level of serum NLRP3 (1.7 ng mL-1) among MI patients compared to controls (0.71 ng mL-1). The 0.75 ng mL-1 considered as a good predictor for MI with ECG findings. Only Q705K and 14229 genetic variant alleles were significantly associated with high NLRP3 protein serum level among MI patients.

Four novel SNPs in exon 3 of NLRP3 gene in addition to previously reported Q705K conferring risk for development of MI among Iraqis. Only variants allele of Q705K and gene position 14229 was associated with elevated serum NLRP3 protein among MI patients.