Haplotype analysis of carnitine transporters and left ventricular mass in human essential hypertension
Haplotype analysis of carnitine transporters and left ventricular mass in human essential hypertension
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DOI：
10.1053/j.jrn.2004.09.035
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Stella, P
中科院分区：
文献类型：
--
作者：
Tripodi, G;Modica, R;Stella, P
目的：心肌脂肪酸代谢的改变可能是高血压左室肥厚（LVH）的分子机制之一。我们测试的假设，即多态性的基因参与肉毒碱运输，OCTN 2，CPT 1A，CPT 1B和CPT 2，可能与LVH.Design：单倍型为基础的关联分析在一项观察性研究。患者：方法：对215例未接受过治疗的中年轻度原发性高血压患者的左室质量指数（LVMI）、左室舒张功能（舒张功能）、左室舒张功能（舒张功能）、左室舒张功能（舒张功能）进行相关性分析。结果：从单核苷酸多态性数据库（dbSNPs）中筛选出覆盖4个基因座基因组区域的SNPs，共鉴定出23种单倍型：OCTN 2（H1至H8）8例，CPT 1A（H9至H16）8例，CPT 1B（H17至H19）3例，CPT 2（H20至H23）4例。在多位点单倍型分析中，在调整了性别、年龄、收缩压、舒张压、体重指数和高血压持续时间后，H13对LVMI有显著影响，（+8.9，P = .05）、H14（-5.63，P = .05）、H15（-18.79，P = .0006）、H18（-1.66，P = .03）和H22（-3.42，P = .004）。这些显著的单倍型分别占总人群的3.7%、1.6%、1.6%、39.3%和29.7%.Conclusions：这些结果确定了肉毒碱转运体基因家族作为高血压患者LVMI的候选调节因子。使用常见的SNP来定义与感兴趣的表型相关的信息性单倍型是朝向鉴定捕获的贡献SNP进展的起点。(C)2005年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
Objective: The carnitine-associated alteration of myocardial fatty acid metabolism may be one of the molecular mechanisms underlying left ventricular hypertrophy (LVH) in essential hypertension. We tested the hypothesis that polymorphisms of the genes involved in carnitine transport, OCTN2, CPT1A, CPT1B, and CPT2, might be associated with LVH.Design: Haplotype-based association analysis in an observational study.Setting: Outpatients from the Nephrology Division of the University Hospital. Patients: A total of 215 never-treated, middle-aged patients with mild essential hypertension.Methods: Relationships between left ventricular mass index (LVMI) (measured with m-mode echocardiography) and haplotype combinations for 13 common genetic variants selected from single nucleotide polymorphism database (dbSNPs).Results: The SNPs were selected to cover the genomic region of the four loci, and a total of 23 haplotypes were identified: 8 for OCTN2 (H1 to H8), 8 for CPT1A (H9 to H16), 3 for CPT1B (H17 to H19), and 4 for CPT2 (H20 to H23). In a multilocus haplotype analysis, after adjusting for sex, age, systolic blood pressure, diastolic blood pressure, body mass index, and duration of hypertension, a significant effect on LVMI was seen for H13 (+8.9, P = .05), H14 (-5.63, P = .05), H15 (-18.79, P = .0006), H18 (-1.66, P = .03), and H22 (-3.42, P = .004). These significant haplotypes were respectively 3.7 %, 1.6 %, 1.6 %, 39.3 %, and 29.7 % of the total population.Conclusions: These results identify the carnitine-transporter gene family as candidate modifiers of LVMI in human hypertension. The use of common SNPs to define informative haplotypes associated with the phenotype of interest is the starting point for progress toward identification of the trapped contributing SNP(s). (C) 2005 by the National Kidney Foundation, Inc.