Measured haplotype analysis of the aldosterone synthase gene and heart size
Measured haplotype analysis of the aldosterone synthase gene and heart size
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DOI：
10.1038/sj.ejhg.5200967
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发表时间：
2003-05-01
影响因子：
5.2
通讯作者：
Farrall, M
中科院分区：
文献类型：
--
作者：
Mayosi, BM;Keavney, B;Farrall, M
心脏大小和醛固酮合成酶（CYP 11B 2）基因的基因关联研究产生了不一致的结果，可能是因为样本量和/或多态性的数量和位置的限制。跨越6 kb的CYP 11B 2基因在高加索英国家庭的多态性分析显示，由于在这个小区域的强烈连锁不平衡的单倍型数量有限。基因型和单倍型信息被用于一项关联研究，涉及229个家族的955名成员，用于心脏大小的超声心动图测量表型。在混合效应线性模型分析中，G5937 C多态性与心壁厚度相关（P = 0.02），内含子转换和A4550 C多态性与左心室腔大小相关（P = 0.02和0.002，分别）。测量的单倍型分析证实了内含子转换和G5937 C多态性与心壁厚度的等位基因（P = 0.02），以及内含子转换多态性与左心室腔大小的等位基因（P = 0.04）。多态性对这些性状变异的贡献率为2.0-3.4%。总之，CYP 11B 2基因的遗传多态性对超声心动图测量心脏大小的定量变化有很小的贡献。这些结果表明，在基因关联研究中，分析遗传变异的全部范围以捕获基因座的单倍型结构是非常重要的。
Gene-association studies of heart size and the aldosterone synthase (CYP11B2) gene have produced inconsistent results, possibly because of limitations in the sample size and/or the number and location of the polymorphisms. An analysis of six polymorphisms spanning 6 kb of the CYP11B2 gene in Caucasian British families revealed a limited number of haplotypes because of strong linkage disequilibrium over this small region. The genotype and haplotype information was used in an association study involving 955 members of 229 families phenotyped for echocardiographic measures of heart size. In a mixed effects linear modelling analysis, the G5937C polymorphism was associated with cardiac wall thickness (P = 0.02), and the intron conversion and A4550C polymorphisms were associated with left ventricular cavity size (P = 0.02 and 0.002, respectively). Measured haplotype analyses confirmed the association of alleles at the intron conversion and G5937C polymorphisms with cardiac wall thickness (P = 0.02), and alleles at the intron conversion polymorphism with left ventricular cavity size (P = 0.04). The polymorphisms contributed to 2.0-3.4% of the variability in these traits. In summary, genetic polymorphisms at the CYP11B2 gene make a small contribution to quantitative variation in echocardiographic measures of heart size. These results point to the importance of analysing the full extent of genetic variation that captures the haplotype structure of a locus in gene association studies.