Endothelial Nitric Oxide Synthase Gene G894T Polymorphism and Myocardial Infarction: A Meta-Analysis of 34 Studies Involving 21068 Subjects

<div><p>Background</p><p>Researches have revealed that the endothelial nitric oxide synthase (<i>eNOS</i>) gene G894T polymorphism is associated with the risk of Myocardial infarction (MI), but the results remain conflicting.</p><p>Objective and Methods</p><p>A meta-analysis was conducted to investigate the association between <i>eNOS</i> G894T polymorphism and MI. Published studies from PubMed, Embase, CNKI and CBM databases were retrieved. The pooled odds ratios (ORs) for the association between <i>eNOS</i> G894T polymorphism and MI and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed- effect model.</p><p>Results</p><p>A total of 34 studies including 8229 cases and 12839 controls were identified for the meta-analysis. The <i>eNOS</i> G894T polymorphism was significantly associated with MI under a homozygous genetic model (OR = 1.41, 95% CI = 1.08–1.84; <i>P</i> = 0.012), a recessive genetic model (OR = 1.35, 95% CI = 1.06–1.70; <i>P</i> = 0.014), a dominant genetic model (OR = 1.18, 95% CI = 1.04–1.34; <i>P</i> = 0.009). In the subgroup analysis by ethnicity (non-Asian and Asian), no significant association was observed between <i>eNOS</i> G894T polymorphism and MI risk among non-Asians (<i>P</i>>0.05), but a positive significant association was found among Asians (<i>P</i><0.05).</p><p>Conclusions</p><p>The <i>eNOS</i> G894T polymorphism is associated with increased MI risk in Asians. The results indicate that ethnicity plays important roles in the association between <i>eNOS</i> G894T polymorphism and MI.</p></div

Pooled ORs and 95% CIs of the association between eNOS G894T polymorphism and MI.

<p>OR: odds ratio; 95% CI: 95% confidence interval. P-value was for pooled ORs. When I²<50%, it was for fixed effect model, otherwise it was for random effect model. Small study: studies with less than 400 participants; Medium study: studies with more than 400 and less than 1000 participants; Large study: studies with more than 1000 participants.</p

Telmisartan PKs of 48 health males with different genotypes.

<p>Data were shown as mean±SD;</p>*<p><i>P</i><0.05; **<i>P</i><0.01.</p><p>PKs, pharmacokinetics; <i>ORM1</i>, orosomucoid 1; <i>ABCC2</i>, ATP-binding cassette, sub-family C, member 2; <i>ABCG2</i>, ATP-binding cassette, sub-family G, member 2; <i>ABCB1,</i> ATP-binding cassette, sub-family B, member 1; <i>SLCO1B3,</i> solute carrier organic anion transporter family, member 1B3; SNP, single nucleotide polymorphisms; AUC_(0–48) the area under the plasma concentration-time curve (AUC) from 0 to 48 h; AUC_(0–∞), AUC from 0 to ∞; C_max, the peak concentration in plasma; CL/F, clearance; T_1/2, elimination half-life; T_max, the time to C_max.</p

Summary of Genetic Variations of SNPs in this Study.

a<p>data published on hapmap; b, data calculated in this study, N = 48; N/A, no data found in hapmap.</p><p>MAF: Minor Allele frequencies; CHB: Han Chinese in Beijing, China; ASW: African ancestry in Southwest USA; CEU: Utah residents with Northern and Western European ancestry from the CEPH collection <i>ORM1</i>, orosomucoid 1; <i>ABCC2</i>, ATP-binding cassette, sub-family C, member 2; <i>ABCG2</i>, ATP-binding cassette, sub-family G, member 2; <i>ABCB1,</i> ATP-binding cassette, sub-family B, member 1; <i>SLCO1B3,</i> solute carrier organic anion transporter family, member 1B3; SNP, single nucleotide polymorphisms; AUC_(0–48) the area under the plasma concentration-time curve (AUC) from 0 to 48 h; AUC_(0–∞), AUC from 0 to ∞; C_max, the peak concentration in plasma; CL/F, clearance; T_1/2, elimination half-life; T_max, the time to C_max.</p

The impacts of <i>ORM1</i> genotypes on the PKs and BP change(%) after 40 mg telmisartan.

<p>A, Concentration; B, AUC_(0–∞); C, SBP change(%) from the baseline; D, DBP change(%) from the baseline.</p