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Q705K variant in NLRP3 gene confers protection against myocardial infarction in female individuals.

ABSTRACT: Inflammation is a multifaceted process that underlies the pathophysiology of acute myocardial infarction (MI). Variations in the inflammasome-related NLRP3 gene have been associated with risk for a number of different inflammatory diseases. Therefore, Q705K polymorphism in NLRP3 gene likely confers susceptibility to risk for MI. A First-ever myocardial Infarction study in Ac-county (FIA) cohort comprising 555 MI patients and 1,016 controls was used to genotype rs35829419 in the NLRP3 gene by TaqMan single-nucleotide polymorphism assay. C-reactive protein (CRP) was measured in the study participants by ELISA. The results showed no significant association between the variant rs35829419 and MI. However, the minor A allele of the rs35829419 polymorphism conferred a protective effect against the risk of developing MI in females. The minor A allele of rs35829419 polymorphism was also associated with increased CRP levels in males. Results of the study suggested a gender-specific deregulation of NLRP3 gene mediated by rs35829419 polymorphism that confers protection against MI in females but has no effect on MI susceptibility in males. However, the rs35829419 polymorphism was associated with increased CRP levels among the male subjects, thereby demonstrating the possible effect of the Q705K polymorphism in elevating the basal active state of innate immune response.

SUBMITTER: Varghese GP

PROVIDER: S-EPMC3917090 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Q705K variant in NLRP3 gene confers protection against myocardial infarction in female individuals.

Varghese Geena Paramel GP Fransén Karin K Hurtig-Wennlöf Anita A Bengtsson Torbjörn T Jansson Jan-Håkan JH Sirsjö Allan A

Biomedical reports 20130807 6

Inflammation is a multifaceted process that underlies the pathophysiology of acute myocardial infarction (MI). Variations in the inflammasome-related NLRP3 gene have been associated with risk for a number of different inflammatory diseases. Therefore, Q705K polymorphism in NLRP3 gene likely confers susceptibility to risk for MI. A First-ever myocardial Infarction study in Ac-county (FIA) cohort comprising 555 MI patients and 1,016 controls was used to genotype rs35829419 in the ...[more]

PMID: 24649046

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Project description:AimsAlthough the reno-protective effects of sodium-glucose cotransporter 2 inhibitors are known in patients with heart failure or type 2 diabetes mellitus (T2DM), this effect has not been confirmed in patients with acute myocardial infarction (AMI).Methods and resultsThe prospective, multicentre, randomized, double-blind, placebo-controlled EMBODY trial investigated patients with AMI and T2DM in Japan. The eligible patients included adults aged 20 years or older, diagnosed with AMI and T2DM, and who could be discharged within 2-12 weeks after the onset of AMI. One hundred and five patients were randomized (1:1) to receive once daily 10 mg empagliflozin or placebo within 2 weeks of AMI onset. In this sub-analysis, we investigated the time course of renal functional parameters such as serum creatinine levels and estimated glomerular filtration rate (eGFR) from baseline to Weeks 4, 12, and 24. Ninety-six patients (64 ± 11 years, 78 male) were included in the full analysis (n = 46 and 50 in the empagliflozin and placebo groups, respectively). We used serum creatinine and eGFR as indicators of renal function. In the placebo group, eGFR decreased from 66.14 mL/min/1.73 m2 at baseline to 62.77 mL/min/1.73 m2 by Week 24 (P = 0.023) but remained unchanged in the empagliflozin group (from 64.60 to 64.36 mL/min/1.73 m2 , P = 0.843). In the latter group, uric acid improved from 5.8 mg/dL at baseline to 4.9 mg/dL at Week 24 (P < 0.001). In the earlier analysis of 56 patients with eGFR ≥ 60 mL/min/1.73 m2 , the eGFR decreased and the serum creatinine increased from baseline to 24 weeks in the placebo group, significantly different to the empagliflozin group (-6.61 vs. +0.22 mL/min/1.73 m2 , P = 0.008 and +0.063 vs. -0.001 mg/dL, P = 0.030, respectively). The changes in serum creatinine and eGFR from baseline to Week 24 were significantly correlated with those in uric acid in the placebo group (r = 0.664, P < 0.001 and r = -0.675, P < 0.001, respectively) but not in the empagliflozin group.ConclusionsEmpagliflozin prevented the kidney functional decline in patients with AMI and T2DM, especially those with baseline eGFR ≥ 60 mL/min/1.73 m2 . Early administration of sodium-glucose cotransporter 2 inhibitors in these patients is considered desirable for renal protection.

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Q705K variant in NLRP3 gene confers protection against myocardial infarction in female individuals.

Publications

Q705K variant in <i>NLRP3</i> gene confers protection against myocardial infarction in female individuals.

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