https://scholars.lib.ntu.edu.tw/handle/123456789/525836
標題: | Genetic epidemiological study doesn't support GLA IVS4?+?919G?>?A variant is a significant mutation in Fabry disease | 作者: | Chiang H.-L. Wang N.H.-H. Song I.-W. Chang C.-P. Wen M.-S. YIN-HSIU CHIEN WUH-LIANG HWU Tsai F.-J. Chen Y.-T. Wu J.-Y. |
公開日期: | 2017 | 出版社: | Academic Press Inc. | 卷: | 121 | 期: | 1 | 起(迄)頁: | 22-27 | 來源出版物: | Molecular Genetics and Metabolism | 摘要: | Background The GLA IVS4?+?919G?>?A which is linked to late-onset Fabry disease shows high frequency in Taiwan. Methods To determine whether IVS4?+?919G?>?A is a frequent cause of heart disease, we genotyped it in normal controls and other disease cohorts (type 2 diabetes, heart failure, ventricular tachycardia, atrial fibrillation and coronary artery disease). Normal controls and diabetes patients carrying the variant were evaluated for their cardiac condition. Minigene constructs were used to study GLA splicing patterns in different cell lines. Results GLA IVS4?+?919A was found in 4/1634 males (0.245%) and 2/1634 females (0.123%) in normal controls and in 4/2133 males (0.188%) and 7/1816 females (0.385%) in the type 2 diabetes cohort. Of all the 17 IVS4?+?919A carriers in these two groups, only two males reported heart-related disease (myocardial infarction and hypertensive heart disease). Furthermore, in the heart disease cohort (n?=?649), only one male carried the variant. Minigene constructs showed that the AGS (stomach) cell line showed a distinct GLA splicing pattern. Conclusion Most subjects carrying GLA IVS4?+?919A did not show abnormal cardiac phenotypes. The near-absence of GLA IVS4?+?919A in heart disease cohort suggested that this variant is not a frequent cause of overt heart diseases in Taiwan and that the genotype-phenotype correlation and natural course of the disease need further investigation. We also showed that the GLA IVS4?+?919G?>?A nucleotide change did influence alternative splicing in a tissue-specific manner. Synopsis The GLA IVS4?+?919G?>?A variant is not a frequent cause of overt heart disease in Taiwan. ? 2017 |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85016399743&doi=10.1016%2fj.ymgme.2017.03.005&partnerID=40&md5=fbd0c1995133c4da55621e2c1cfe40ea https://scholars.lib.ntu.edu.tw/handle/123456789/525836 |
ISSN: | 1096-7192 | DOI: | 10.1016/j.ymgme.2017.03.005 | SDG/關鍵字: | alpha galactosidase; alpha galactosidase; alpha-galactosidase A, human; adult; aged; alternative RNA splicing; Article; atrial fibrillation; controlled study; coronary artery disease; Fabry disease; female; gene mutation; genetic epidemiology; genetic variability; genotype; genotype phenotype correlation; heart failure; heart infarction; heart ventricle tachycardia; human; human cell; hypertension; major clinical study; male; non insulin dependent diabetes mellitus; priority journal; animal; cell line; Chlorocebus aethiops; cohort analysis; complication; CV-1 cell line; epidemiology; Fabry disease; genetics; heart disease; HEK293 cell line; K-562 cell line; MCF-7 cell line; middle aged; mutation; newborn; Taiwan; Adult; Aged; alpha-Galactosidase; Alternative Splicing; Animals; Cell Line; Cercopithecus aethiops; Cohort Studies; COS Cells; Fabry Disease; Female; Heart Diseases; HEK293 Cells; Humans; Infant, Newborn; K562 Cells; Male; MCF-7 Cells; Middle Aged; Mutation; Taiwan |
顯示於: | 醫學系 |
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