位于1号染色体q臂上的钙蛋白酶2/钙蛋白酶8基因座与血清α-胡萝卜素浓度的变化相关。
The CAPN2/CAPN8 Locus on Chromosome 1q Is Associated with Variation in Serum Alpha-Carotene Concentrations.
作者信息
D'Adamo Christopher R, Dawson Valerie J, Ryan Kathleen A, Yerges-Armstrong Laura M, Semba Richard D, Steinle Nanette I, Mitchell Braxton D, Shuldiner Alan R, McArdle Patrick F
机构信息
Department of Family & Community Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
出版信息
J Nutrigenet Nutrigenomics. 2016;9(5-6):254-264. doi: 10.1159/000452890. Epub 2016 Dec 22.
BACKGROUND/AIMS: Alpha-carotene is a provitamin A carotenoid present in fruits and vegetables. Higher serum concentrations of α-carotene have been associated with lower risk of cancer and all-cause mortality. Previous studies have suggested that genetic variants influence serum concentrations of provitamin A carotenoids, but to date no variants have been robustly associated with serum α-carotene concentrations. The aim of this study was to identify genetic associations with serum α-carotene concentrations using the genome-wide association study (GWAS) approach.
METHODS
A GWAS of serum α-carotene concentrations was conducted in 433 Old Order Amish adults who had consumed a 6-day controlled diet. Linear regression models adjusting for age, gender, and family structure were utilized to evaluate associations between genetic variants and serum α-carotene concentrations.
RESULTS
Genome-wide significant associations with α-carotene concentrations were observed for loci on chromosome 1q41 between the genes CAPN2 and CAPN8 (rs12137025, p = 3.55 × 10-8), chromosome 2p21 in PRKCE (rs2594495, p = 1.01 × 10-8), and chromosome 4q34 (rs17830069, p = 2.89 × 10-8).
CONCLUSIONS
We identified 3 novel loci associated with serum α-carotene concentrations among a population that consumed a controlled diet. While replication is necessary, the CAPN2/CAPN8 locus provides compelling evidence for an association with serum α-carotene concentrations and may suggest a relationship with the development and progression of cancers.
背景/目的：α-胡萝卜素是一种存在于水果和蔬菜中的维生素A原类胡萝卜素。血清中α-胡萝卜素浓度较高与较低的癌症风险和全因死亡率相关。既往研究表明，基因变异会影响维生素A原类胡萝卜素的血清浓度，但迄今为止，尚无变异与血清α-胡萝卜素浓度存在稳健关联。本研究的目的是采用全基因组关联研究（GWAS）方法确定与血清α-胡萝卜素浓度相关的基因关联。
方法
对433名食用了6天控制饮食的旧秩序阿米什成年人进行了血清α-胡萝卜素浓度的GWAS。采用调整了年龄、性别和家庭结构的线性回归模型来评估基因变异与血清α-胡萝卜素浓度之间的关联。
结果
在第1号染色体q41区域位于CAPN2和CAPN8基因之间的位点（rs12137025，p = 3.55×10-8）、第2号染色体p21区域PRKCE基因中的位点（rs2594495，p = 1.01×10-8）以及第4号染色体q34区域（rs17830069，p = 2.89×10-8）观察到与α-胡萝卜素浓度存在全基因组显著关联。
结论
我们在食用控制饮食的人群中确定了3个与血清α-胡萝卜素浓度相关的新位点。虽然有必要进行重复验证，但CAPN2/CAPN8位点为与血清α-胡萝卜素浓度的关联提供了有力证据，并可能提示与癌症的发生和发展存在关联。
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