کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2893790 1172420 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Frequency and function of CETP variants among individuals of Asian ancestry
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Frequency and function of CETP variants among individuals of Asian ancestry
چکیده انگلیسی

Genetic variation in CETP (cholesteryl ester transfer protein) has been clearly associated with HDL cholesterol levels but its association with cardiovascular disease and related phenotypes has been more controversial, possibly due to variability of polymorphisms and their frequencies across different ethnic populations. To see if there are undetected polymorphisms affecting protein sequence in individuals of Asian ancestry and to determine the functionality of such variants, all exons and adjacent intronic segments were resequenced in 96 individuals and the observed variants cloned and analyzed. Two novel SNPs, including one coding change, S332 to Y332, were identified. Y332 and all other reported variants in Asians were cloned for study in vitro. Secretion efficiency was determined by Western blotting of protein from cell lysates and media. Cholesteryl ester transfer activity was measured in vitro by following the extent of transfer of fluorescently labeled substrate. Y332, Q296 and G442 are all secreted less well than wild type protein but retain significant transfer activity. P151 is not secreted and no transfer activity was detected. These protein variants should all contribute to higher HDL cholesterol in individuals carrying them. Additionally, a splicing variation that causes a protein truncation and non-functional CETP that has been reported predominantly in Asians was also found in two individuals of European ancestry and was on the same haplotype background in the two populations, suggesting a common origin of this null variant. This improved understanding of CETP variation in Asians will allow a more effective comparison of studies across populations.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 202, Issue 1, January 2009, Pages 241–247
نویسندگان
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