Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia
Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia
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DOI：
10.1161/atvbaha.107.160150
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发表时间：
2008-06-01
影响因子：
8.7
通讯作者：
Lusis, Aldons J.
中科院分区：
文献类型：
--
作者：
Mar-Heyming, Rebecca;Miyazaki, Makoto;Lusis, Aldons J.
β-硬脂酰辅酶A去饱和酶1（SCD 1）是参与单不饱和脂肪酸合成的限速酶，在小鼠中，SCD 1活性与血浆甘油三酯水平相关。我们使用脂肪酸去饱和指数（血浆18：1/18：0的比率）作为SCD 1活性的标志物来研究SCD 1与家族性混合型高脂血症（FCHL.Methods and Results）的关系。FCHL患者与无关对照组相比，SCD 1活性增加（P < 0.0001）。在本研究样本中，发现脂肪酸去饱和指数具有高度遗传性（h（2）= 0.48，P = 2.2 x 10（-11））。对来自18个FCHL家系的346个同胞对的QTL分析表明，去饱和指数与染色体3p26.1至3 p13连锁（z = 2.7，P = 0.003），含有过氧化物酶体增殖物激活受体γ 20 p11.21 ~ 20 q13.32（z = 1.7，P = 0.04），含有肝细胞核因子4 α（HNF 4 α）基因。HNF 4 α的一个特定的单倍型被发现与这些FCHL家族中的去饱和指数相关（P = 0.002）。结论我们的研究结果表明，脂肪酸去饱和指数是一个高度遗传的性状，与FCHL中观察到的血脂异常相关。
Objective-Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme involved in the synthesis of monounsaturated fatty acids, and in mice SCD1 activity is associated with plasma triglyceride levels. We used the fatty acid desaturation index (the plasma ratio of 18:1/18:0) as a marker of SCD1 activity to investigate the relationship of SCD1 to familial combined hyperlipidemia (FCHL).Methods and Results-The fatty acid desaturation index was measured in 400 individuals from 18 extended FCHL pedigrees. FCHL-affected individuals exhibited increased SCD1 activity when compared to unrelated controls (P < 0.0001). The fatty acid desaturation index was found to be highly heritable (h(2) = 0.48, P = 2.2 x 10(-11)) in this study sample. QTL analysis in 346 sibling pairs from 18 FCHL families revealed suggestive linkage of the desaturation index to chromosomes 3p26.1 to 3p13 (z = 2.7, P = 0.003), containing the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene, and 20p11.21 to 20q13.32 (z = 1.7, P = 0.04), containing the hepatocyte nuclear factor 4, alpha (HNF4 alpha) gene. A specific haplotype of HNF4 alpha was found to be associated with the desaturation index in these FCHL families (P = 0.002).Conclusion-Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL.