Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia.
Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia.
复制标题
人类 PPARa 基因的分子扫描：L162v 突变与高脱脂β脂蛋白血症的关联。
作者：
M. Vohl;P. Lepage;D. Gaudet;C. Brewer;C. Bétard;P. Perron;G. Houde;Christine Cellier;J. Faith;J. Despres;K. Morgan;T. Hudson
过氧化物酶体增殖物激活受体α（PPARalpha）是参与控制细胞脂质利用的类固醇激素受体超家族的成员。这使得PPARalpha成为2型糖尿病和血脂异常的候选基因。本研究的目的是调查人类PPARalpha基因的遗传变异是否会影响法裔加拿大人患2型糖尿病和血脂异常的风险。因此，我们首先确定了人类PPARalpha的基因组结构，然后设计内含子引物对12例2型糖尿病患者和2例非糖尿病受试者的编码区和外显子-内含子边界进行测序。序列分析显示，存在L162 V错义突变的外显子5的糖尿病患者。亮氨酸162包含在人PPARalpha基因的DNA结合结构域中，并且在人、小鼠、大鼠和豚鼠中是保守的。随后，我们筛选了121例新诊断为2型糖尿病的患者及其年龄和性别匹配的非糖尿病对照组，这些患者来自魁北克东北部的Saguenay-Lac-St-Jean地区，通过基于PCR-RFLP的方法筛选L162 V突变的存在。糖尿病患者与非糖尿病患者的L162纯合子和V162携带者频率无差异。然而，无论是否患有糖尿病，V162等位基因携带者的血浆载脂蛋白B水平均高于非携带者（P5 0.05）。为了进一步研究这种关联，我们筛选了另一个在大魁北克市招募的193名非糖尿病受试者样本。V162等位基因携带者的血浆总脂蛋白、LDL-载脂蛋白B和LDL胆固醇浓度显著高于L162等位基因纯合子（P </= 0.02）。这些结果表明PPARalpha V162等位基因与致动脉粥样硬化/高载脂蛋白B血脂异常之间存在关联。
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the steroid hormone receptor super family involved in the control of cellular lipid utilization. This makes PPARalpha a candidate gene for type 2 diabetes and dyslipidemia. The aim of this study was to investigate whether genetic variation in the human PPARalpha gene can influence the risk of type 2 diabetes and dyslipidemia among French Canadians. We therefore first determined the genomic structure of human PPARalpha, and then designed intronic primers to sequence the coding region and the exon-intron boundaries of the gene in 12 patients with type 2 diabetes and in 2 nondiabetic subjects. Sequence analysis revealed the presence of a L162V missense mutation in exon 5 of one diabetic patient. Leucine 162 is contained within the DNA binding domain of the human PPARalpha gene, and is conserved among humans, mice, rats, and guinea pigs. We subsequently screened a sample of 121 patients newly diagnosed with type 2 diabetes and their age and sex-matched nondiabetic controls, recruited from the Saguenay-Lac-St-Jean region of Northeastern Quebec, for the presence of the L162V mutation by a PCR-RFLP based method. There was no difference in L162 homozygote or V162 carrier frequencies between diabetics and nondiabetics. However, whether diabetic or not, carriers of the V162 allele had higher plasma apolipoprotein B levels compared to noncarriers (P 5 0.05). To further this association, we screened another sample of 193 nondiabetic subjects recruited in the greater Quebec City area. Carriers of the V162 allele compared with homozygotes of the L162 allele had significantly higher concentrations of plasma total and LDL-apolipoprotein B as well as LDL cholesterol (P </= 0.02). These results suggest an association between the PPARalpha V162 allele and the atherogenic/hyperapolipoprotein B dyslipidemia.
影响因子：
15.9
作者：
Djouadi, F;Weinheimer, CJ;Kelly, DP
通讯作者：
Kelly, DP
油酸和吉非贝齐对培养肝细胞三酰甘油和磷脂酰胆碱生物合成和分泌的差异影响的酶学解释。
DOI：
10.1016/0005-2760(93)90140-5
发表时间：
1993
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Lamb,RG;Koch,JC;Bush,SR
通讯作者：
Bush,SR
影响因子：
15.9
作者：
VidalPuig, AJ;Considine, RV;Flier, JS
通讯作者：
Flier, JS