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paraoxonase gene cluster variations associated with coronary heart disease in Chinese Han women

Chinese Medical Journal 2005年第14期118卷 1167-1174页

作者： SUShao-yong CHENJian-hong HUANGJian-feng WANGXiao-ling ZHAOJian-gong SHENYan QIANGBo-qin GUDong-feng DivisionofPopulationgenetics CardiovascularInstituteandFuWaiHospitalChineseAcademyofMedicalSciencesandPekingUnionMedicalCollegeBeijing100037China NationalHumanGenomeCenter Beijing3-707NorthYongchangRd.Beijing100176China

Background The oxidative modification of low-density lipoprotein in theartery wall is currently believed to be central to the pathogenesis of atherosclerosis. paraoxonase(PON1), an enzyme located on high-density lipoprotein (HDL) , can prevent low-density lipoprotein(LDL) from oxidation at a certain extent. Recent studies show two other members of paraoxonase genefamily, PON2 and PON3, possess antioxidant properties similar to PON1. The aim of the present studywas to explore the role of PON gene cluster on coronary heart disease (CHD) in Chinese Han *** Seven polymorphisms including PON1 -107C > T, -162G > A, -831G > A, R160G, Q192R, PON2S311C, and PON3 -133C > A were genotyped in 184 female patients with CHD and 239 female *** plasma PON1 activity toward phenylacetate was determined in 50 cases and 50 controls randomlyselected. Results The plasma PON1 activities were significantly lower in cases than in *** SNP analysis showed that cases had significantly higher frequencies of PON1 -107T, -831Gand PON2 311S alleles than controls. The genotype distributions of -107C >T were also significantlydifferent between two groups. The odds ratios for the development of CHD were 1. 66 for -107TCcarriers and 2. 0 for -107TT carriers, compared with -107CC carriers. Haplotype analyses showed thatthe distributions of haplotypes comprised of PON1 -107C > T and PON2 S311C were significantlydifferent between cases and controls, with cases having higher frequency of T-S haplotype (44.8% vs.36.3%, P =0.013). The T-S haplotype remained significantly associated with CHD after adjustingenvironmental risk factors (P = 0.0069). Conclusions This association study suggested that lowerplasma PON1 activity increased the risk of CHD in Chinese woman, which may be mediated by the higherfrequency of -107T allele in cases. Haplotype analyses indicated that there might be somesynergistic effects between the PON1 -107C > T and PON2 S311C polymorphisms.

关键词： coronary heart disease paraoxonase gene cluster paraoxonase chinese hanwomen

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Human paraoxonase gene cluster overexpression alleviates angiotensin II-induced cardiac hypertrophy in mice

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Science China(Life Sciences) 2016年第11期59卷 1115-1122页

作者： Jian-Fei Pei Yun-Fei Yan Xiaoqiang Tang Yang Zhang Shen-Shen Cui Zhu-Qin Zhang Hou-Zao Chen De-Pei Liu State Key Laboratory of Medical Molecular Biology Department of Biochemistry and Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical College

Cardiac hypertrophy is the strongest predictor of the development of heart failure, and anti-hypertrophic treatment holds the key to improving the clinical syndrome and increasing the survival rates for heart failure. The paraoxonase(PON) gene cluster(PC) protects against atherosclerosis and coronary artery diseases. However, the role of PC in the heart is largely unknown. To evaluate the roles of PC in cardiac hypertrophy, transgenic mice carrying the intact human PON1, PON2, and PON3 genes and their flanking sequences were studied. We demonstrated that the PC transgene(PC-Tg) protected mice from cardiac hypertrophy induced by Ang II; these mice had reduced heart weight/body weight ratios, decreased left ventricular wall thicknesses and increased fractional shortening compared with wild-type(WT) control. The same protective tendency was also observed with an Apoe^(-/-)background. Mechanically, PC-Tg normalized the disequilibrium of matrix metalloproteinases(MMPs)/tissue inhibitors of MMPs(TIMPs) in hypertrophic hearts, which might contribute to the protective role of PC-Tg in cardiac fibrosis and, thus, protect against cardiac remodeling. Taken together, our results identify a novel anti-hypertrophic role for the PON gene cluster, suggesting a possible strategy for the treatment of cardiac hypertrophy through elevating the levels of the PON gene family.

关键词： cardiac hypertrophy fibrosis paraoxonase gene cluster angiotensin II

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