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- Axelsson, Irene, et al.
(författare)
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The influence of dietary nucleotides on erythrocyte membrane fatty acids and plasma lipids in preterm infants
- 1997
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 86:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to evaluate whether a regular formula for premature infants supplemented with nucleotides has any influence on plasma lipids and erythrocyte membrane fatty acids. METHODS: Preterm infants fed either human milk supplemented with human milk protein (HM, n = 14), nucleotide-supplemented preterm formula (NF, n = 13), or a regular preterm formula (F, n = 13) were included in the study. The NF was supplemented with 18.2 mg cytidine monophosphate/l (CMP), 7.0 mg uridine monophosphate/l (UMP), 6.4 mg adenosine monophosphate/l (AMP), 3.0 mg inosine monophosphate/l (IMP) and 3.0 mg guanosine monophosphate/l (GMP). RESULTS: There were significantly higher concentrations of triglycerides (TG) in infants fed NF compared to those fed F (191.42 +/- 79.58 vs 108.21 +/- 43.73, p < 0.001, mean +/- SD lipid concentrations, mg/100 ml plasma). Infants fed F had significantly lower concentrations of total cholesterol (94.34 +/- 11.71 vs 115.69 +/- 39.29, p < 0.01) and TG in plasma (108.21 +/- 43.73 vs 172.27 +/- 68.19, p < 0.001, mean +/- SD lipid concentrations, mg/100 ml plasma) when compared to HM-fed infants. There were no significant differences in any of the erythrocyte membrane fatty acids and total long-chain polyunsaturated fatty acids (LC-PUFA) between NF and F during the study period (6 weeks). Furthermore, total LC-PUFA and docosahexaenoic acid (DHA) concentrations in red blood cell were not significantly different when infants fed NF were compared to those fed HM. In contrast, however, infants fed F had significantly lower concentrations of total n-3 LC-PUFA (p < 0.01) and DHA (p < 0.01) than those found in HM-fed infants. CONCLUSIONS: These results do not suggest an effect of nucleotides on the red blood cell LC-PUFA profile in preterm infants. However, the nucleotides may increase the concentrations of triglycerides in plasma.
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| 3. |
- Perera, Minoli A., et al.
(författare)
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Genetic variants associated with warfarin dose in African-American individuals : a genome-wide association study
- 2013
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 382:9894, s. 790-796
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Tidskriftsartikel (refereegranskat)abstract
- Background VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. Methods We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged >= 18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 -1639G -> A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5x10(-8) in the discovery cohort and p<0.0038 in the replication cohort. Findings The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1.51x10(-8)). This association was confirmed in the replication cohort (p=5.04x10(-5)); analysis of the two cohorts together produced a p value of 4.5x10(-12). Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6.92 mg/week and those homozygous 9.34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). Interpretation A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3. Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population.
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