کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2893218 1172409 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Assessment of the association between genetic polymorphisms in transforming growth factor beta, and its binding protein (LTBP), and the presence, and expansion, of Abdominal Aortic Aneurysm
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Assessment of the association between genetic polymorphisms in transforming growth factor beta, and its binding protein (LTBP), and the presence, and expansion, of Abdominal Aortic Aneurysm
چکیده انگلیسی

ObjectivesAbdominal Aortic Aneurysm (AAA) has a strong genetic predisposition. Transforming growth factor beta 1 (TGF-β1) is a causal factor in ascending aortic dilatation; however, a role in AAA pathology is unclear. The aim of the study was to determine whether genes coding TGF-β and its binding protein are associated with the presence and expansion of AAA.MethodsFour geographically distinct case control studies, totaling 1890 AAA cases and 3785 controls, were genotyped and compared to the presence, size and growth rate of AAA. 26 single nucleotide polymorphisms (SNPs) in 5 genes were genotyped in the UK cohort and the result was replicated in 3 independent cohorts.ResultsNo associations between genotypes or haplotypes and the presence of AAA disease were confirmed. Five SNPs in Latent TGF-β Binding Protein (LTBP4) and an allelic variant of TGFB3 were associated with a significant decrease in AAA growth (p ≤ 0.02), in the UK cohort. Altered growth was demonstrated in carriers of two common haplotypes of LTBP4 (+0.38 mm/year, p = 0.003; −0.41 mm/year, p = 0.02, per haplotype copy) and a single haplotype of TGFB3 (−0.53 mm/year, p = 0.05). This association with AAA growth could not be demonstrated in two other independent cohorts. Meta-analysis of AAA size and growth rates in larger AAA (≥45 mm), in all four cohorts, demonstrated a significant association with the LTBP4 21011A > T genotype (a 2% decrease in AAA diameter, or a 0.53 mm/year reduction in AAA growth rate, per T allele [p = 0.03, p = 0.01]).ConclusionThis study suggests that the LTBP4 gene may contribute to AAA progression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 209, Issue 2, April 2010, Pages 367–373
نویسندگان
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