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. 2021 Jun;22(8):451-464.
doi: 10.2217/pgs-2021-0006. Epub 2021 May 4.

NAMPT single-nucleotide polymorphism rs1319501 and visfatin/NAMPT affect nitric oxide formation, sFlt-1 and antihypertensive therapy response in preeclampsia

Daniela A Pereira  1 , Valeria C Sandrim  2 , Ana C Palei  3 , Lorena M Amaral  4 , Vanessa A Belo  1 , Riccardo Lacchini  5 , Ricardo C Cavalli  6 , Jose E Tanus-Santos  7 , Marcelo R Luizon  1   8
Affiliations

NAMPT single-nucleotide polymorphism rs1319501 and visfatin/NAMPT affect nitric oxide formation, sFlt-1 and antihypertensive therapy response in preeclampsia

Daniela A Pereira et al. Pharmacogenomics. 2021 Jun.

Abstract

Aim: We examined the relationships between visfatin/NAMPT and nitrite concentrations (a marker of nitric oxide [NO] formation) or sFlt-1 levels in 205 patients with preeclampsia (PE) responsive or nonresponsive to antihypertensive therapy, and whether NAMPT SNPs rs1319501 and rs3801266 affect nitrite concentrations in PE and 206 healthy pregnant women. Patients & methods: Circulating visfatin/NAMPT and sFlt-1 levels were measured by ELISA, and nitrite concentrations by using an ozone-based chemiluminescence assay. Results: In nonresponsive PE patients, visfatin/NAMPT levels were inversely related to nitrite concentrations and positively related to sFlt-1 levels. NAMPT SNP rs1319501 affected nitrite concentrations in nonresponsive PE patients and was tightly linked with NAMPT functional SNPs in Europeans. Conclusion:NAMPT SNP rs1319501 and visfatin/NAMPT affect NO formation, sFlt-1 levels and antihypertensive therapy response in PE.

Keywords: antihypertensive agents; genetic polymorphisms; nicotinamide phosphoribosyltransferase; nitric oxide; pharmacogenetics; preeclampsia; sFlt-1; visfatin/NAMPT.

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Figures

Figure 1.
Figure 1.. Correlations between plasma nitrite concentrations (A & B) or sFlt-1 (C & D) and visfatin/NAMPT levels in patients with preeclampsia classified as responsive and nonresponsive to antihypertensive therapy.
The regression lines are plotted. The r- and p-values are reported. r: Spearman’s correlation.
Figure 2.
Figure 2.. Plasma nitrite concentrations in healthy pregnant women & patients with preeclampsia grouped by their genotypes for the NAMPT SNPs: (A) rs1319501 T>C and (B) rs3801266 A>G.
The box and whiskers plots show range and quartiles. The boxes extend from the 25th percentile to the 75th percentile, with a line at the median. The whiskers show the highest and lowest values.
Figure 3.
Figure 3.. Plasma nitrite concentrations in patients with preeclampsia classified as responsive or nonresponsive to antihypertensive therapy and grouped by their genotypes for the NAMPT SNPs: (A) rs1319501 T>C and (B) rs3801266 A>G.
The box and whiskers plots show range and quartiles. The boxes extend from the 25th percentile to the 75th percentile, with a line at the median. The whiskers show the highest and lowest values. *p < 0.05 versus TC + CC genotypes.
Figure 4.
Figure 4.. Linkage disequilibrium among SNPs in the NAMPT promoter region for (A) African and (B) European populations.
The numbers below the rs IDs correspond to the number of SNPs found in this genomic region for these populations. Values for pairwise D´ are presented in each box; those without values refer to D′ = 1. Color scheme: bright red, D′ = 1 and LOD ≥2; blue, D′ = 1 and LOD <2; white, D′ <1 and LOD <2. LOD: Logarithm of odds.
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