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951.
Weilai Dong Karen H.Y. Wong Youbin Liu Michal Levy-Sakin Wei-Chien Hung Mo Li Boyang Li Sheng Chih Jin Jungmin Choi Francesc Lopez-Giraldez Dedeepya Vaka Annie Poon Catherine Chu Richard Lao Melek Balamir Irina Movsesyan Mary J. Malloy Hongyu Zhao Clive R. Pullinger 《Journal of lipid research》2022,63(6):100209
Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4–36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those with the highest prevalence of damaging variants were ABCA1 (n = 20), STAB1 (n = 9), OSBPL1A (n = 8), CPS1 (n = 8), CD36 (n = 7), LRP1 (n = 6), ABCA8 (n = 6), GOT2 (n = 5), AMPD3 (n = 5), WWOX (n = 4), and IRS1 (n = 4). Binomial analysis for damaging missense or loss-of-function variants identified the ABCA1 and LDLR genes at genome-wide significance. In conclusion, whole-exome sequencing of individuals with low HDL-C showed the burden of damaging rare variants in the ABCA1 and LDLR genes is particularly high and revealed numerous occurrences in HDL candidate genes, including many genes identified in genome-wide association study reports. Many of these genes are involved in cancer biology, which accords with epidemiologic findings of the association of HDL deficiency with increased risk of cancer, thus presenting a new area of interest in HDL genomics. 相似文献
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BackgroundKennedy’s disease/Spinobulbar muscular atrophy (KD/SBMA) is a degenerative
neuromuscular disease affecting males. This disease is caused by polyglutamine
expansion mutations of the androgen receptor (AR) gene. Although
KD/SBMA has been traditionally considered a motor neuron disease, emerging
evidence points to a central etiological role of muscle. We previously reported a
microarray study of genes differentially expressed in muscle of three genetically
unique mouse models of KD/SBMA but were unable to detect those which are
androgen-dependent or are associated with onset of symptoms.Conclusions/SignificanceBy comparing the current results with those from the three previously reported
models we were able to identify KD/SBMA candidate genes that are androgen
dependent, and occur early in the disease process, properties which are promising
for targeted therapeutics. 相似文献
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K313, a novel benzoxazole derivative,exhibits anti‐inflammatory properties via inhibiting GSK3β activity in LPS‐induced RAW264.7 macrophages 下载免费PDF全文
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Xianfu Zhang Qiang Liu Aiijun Son Qihang Zhang Fushi Zhang Fuqun Zhao 《Photochemical & photobiological sciences》2008,7(3):299-302
The UV/Vis absorption and fluorescence properties of dibenzofluorescein (DBFL) in organic solvents were measured and used to shed light on the possible presence of its tautomers or various prototropic forms. DBFL in aprotic solvents mainly exists in two tautomeric forms, viz. quinoid and lactone, but neither are efficiently fluorescent. In protic solvents, such as methanol and ethanol, both the monoanion and neutral quinoid are present and showed the highest fluorescence quantum yield. In contrast, DBFL is fully dissociated to the monoanion and dianion in deionized water. 相似文献