Goodarzi Mark O, Taylor Kent D, Jones Michelle R, Fang Belle, Guo Xiuqing, Xiang Anny H, Buchanan Thomas A, Hodis Howard N, Raffel Leslie J, Rotter Jerome I
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Atherosclerosis. 2009 Aug;205(2):503-5. doi: 10.1016/j.atherosclerosis.2008.12.038. Epub 2009 Jan 9.
Diabetes and atherosclerosis may share common genetic determinants. A prior study in Hispanics found association of haplotypes in the diabetes gene calpain-10 (CAPN10) with carotid artery intima-media thickness (CIMT). This study sought to replicate this association in an independent cohort.
Four CAPN10 SNPs were genotyped and haplotypes determined in 487 Hispanic Americans from 143 families ascertained via an index case with hypertension. CIMT was measured from B-mode ultrasound, and glycemic traits quantified from euglycemic clamps. Association of SNPs and haplotypes with CIMT was determined.
The minor alleles of SNP-56 and SNP-63 were associated with increased CIMT in dominant and additive models. The association of haplotype 1112 with increased CIMT was replicated. No associations with fasting insulin, insulin secretion, or insulin sensitivity were observed.
CAPN10 association with CIMT was replicated, further supporting its role as a common genetic determinant of diabetes and atherosclerosis in Hispanics.
糖尿病与动脉粥样硬化可能具有共同的遗传决定因素。先前一项针对西班牙裔人群的研究发现,糖尿病基因钙蛋白酶-10(CAPN10)中的单倍型与颈动脉内膜中层厚度(CIMT)有关联。本研究旨在在一个独立队列中重复这一关联。
对来自143个家庭的487名西班牙裔美国人进行了4个CAPN10单核苷酸多态性(SNP)的基因分型并确定单倍型,这些家庭是通过一名高血压指数病例确定的。通过B型超声测量CIMT,并通过正常血糖钳夹技术对血糖特征进行量化。确定SNP和单倍型与CIMT的关联。
在显性和加性模型中,SNP-56和SNP-63的次要等位基因与CIMT增加有关联。单倍型1112与CIMT增加的关联得到了重复验证。未观察到与空腹胰岛素、胰岛素分泌或胰岛素敏感性的关联。
CAPN10与CIMT的关联得到了重复验证,进一步支持了其作为西班牙裔人群中糖尿病和动脉粥样硬化共同遗传决定因素的作用。