The interaction between flavonoids and proteins has attracted great interest among researchers. However, few reports have focused on the structure-affinity relationship of flavonoids binding to proteins. This work mainly concerns the effect of glycosylation of flavonoids on the affinities for BSA. Four flavonoid aglycones (baicalein, quercetin, daidzein, and genistein) and their monoglycosides (baicalin, quercitrin, daidzin, and puerarin, genistin) and another poly glycoside (rutin) are studied for their affinities for BSA. The glycosylation of flavonoids significantly affects the quenching/binding process. In general, the glycosylation of flavonoids lowers the affinity for BSA by 1 to 3 orders of magnitude depending on the conjugation site and the class of sugar moiety. The glucopyranosylation (daidzin and genistin) of flavonoids lowered the affinity for BSA by 5-10 times. Rhamnosylation (quercitrin) of flavonoids, however, lowered the affinity for BSA by 5600 times. This result partly supports that flavonoid aglycones are more easily absorbed than flavonoid glycosides. Higher binding affinities for BSA are associated with higher antioxidant activities for flavonoids. Glycosylation also decreases the hydrophobicity of flavonoids, and hydrophobic interaction may play an important role in binding flavonoids to proteins.
In chronic hypertensive patients, the correlation between blood pressure (BP) and target organ damage, cardiovascular risk, and prognosis is closer for ambulatory BP monitoring (ABPM) than for clinical measurements. So far, most studies have been performed with ABPM for 24 hours. Thus, the criteria for diagnosis of hypertension, mainly based on mean BP values, have been established from data gathered at 15 to 30-min intervals for just one day. Sampling requirements for BP, however, have not been carefully taken into consideration. We have examined the impact of duration and frequency of BP sampling in the reproducibility of mean BP values. We studied 2603 patients with grade 1–2 essential hypertension (1257 men) and a control group of 917 normotensive volunteers (495 men), 51.9±13.8 years of age. ABPM was performed at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. BP series were decimated to generate shorter series with data sampled at 1, 2, 3, or 4-hour intervals for 48 hours, as well as at the original sampling rate for just the first 24 hours. Bland-Altman plots indicate that the diurnal, nocturnal and 24-hour means of BP obtained from the original BP series are better reproduced with data sampled up to 3-hour intervals for 48 hours than by data sampled at 20–30 minute intervals for just one day. The range of the difference in the estimation of the 24-hour mean BP value between the original and the decimated series was about 15 mm Hg for data sampled every 3 hours. This range increased to an unacceptable very high 38 mm Hg (−18 to 20 mm Hg) for data sampled every 20–30 min for just 24 hours. The amount of potential error in the estimation of the daily mean was similar for the second 24 hours of sampling (−21 to 18 mm Hg). This study demonstrates that reproducibility of mean BP values is mainly dependent on duration of sampling but not on sampling rate. Results further indicate that, due to a poor estimation of the true mean BP value, ABPM for 24 hours seem to be insufficient for a proper diagnosis of hypertension and for the evaluation of treatment efficacy. Am J Hypertens (2004) 17, 42A–42A; doi: 10.1016/j.amjhyper.2004.03.101
Abstract Recent studies have shown the ubiquity of pleiotropy for variants affecting human complex traits. These studies also show that rare variants tend to be less pleiotropic than common ones, suggesting that purifying natural selection acts against highly pleiotropic variants of large effect. Here, we investigate the mean frequency, effect size and recombination rate associated with pleiotropic variants, and focus particularly on whether highly pleiotropic variants are enriched in regions with putative strong background selection. We evaluate variants for 41 human traits using data from the NHGRI-EBI GWAS Catalog, as well as data from other three studies. Our results show that variants involving a higher degree of pleiotropy tend to be more common, have larger mean effect sizes, and contribute more to heritability than variants with a lower degree of pleiotropy. This is consistent with the fact that variants of large effect and frequency are more likely detected by GWAS. Using data from four different studies, we also show that more pleiotropic variants are enriched in genome regions with stronger background selection than less pleiotropic variants, suggesting that highly pleiotropic variants are subjected to strong purifying selection. From the above results, we hypothesized that a number of highly pleiotropic variants of low effect/frequency may pass undetected by GWAS.
