Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels.

Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels.
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DOI:
10.1186/1475-2840-11-123
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发表时间:
2012-10-08
影响因子:
9.3
通讯作者:
Li M
Li M
中科院分区:
医学1区
文献类型:
--
作者:
Yin RX;Wu DF;Miao L;Aung LH;Cao XL;Yan TT;Long XJ;Liu WY;Zhang L;Li M

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关于单核苷酸多态(SNPs)和超重/肥胖对血脂谱影响的信息仍然很少。本研究旨在检测10个SNPs及其与超重/肥胖的交互作用对血脂水平的影响。从我们先前分层随机整群抽样中随机抽取978名白骨瑶正常体重和751名超重/肥胖受试者。正常体重、超重和肥胖分别定义为体重指数(BMI;24、24-28和28 kg/m2)。测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、载脂蛋白A1(ApoA1)和载脂蛋白B(ApoB)水平。ATP结合盒转运体A1(ABCA-1)V825I、酰基辅酶A:胆固醇酰基转移酶-1(ACAT-1)rs1044925、低密度脂蛋白受体(LDL-R)AvaII、肝脂酶基因(LIPC)-250G;A、内皮脂肪酶基因(LIPG)584C&gT;T、亚甲基四氢叶酸还原酶(MTHFR)677C&gT;T、E3泛素连接酶肌球蛋白轻链相互作用蛋白(MYLIP)rs3757354、原蛋白转化枯草杆菌样蛋白9型(PCSK9)E670G、过氧化物酶激活受体Delta(PPARD)+294T&GT;C和清道夫受体B类1(SCARB1)rs5888通过聚合酶链式反应和限制性片段长度多态性结合凝胶电泳法进行扩增,然后直接测序证实。交互作用用析因设计协方差分析进行检验。正常体重和超重/肥胖者LIPC和PCSK9的基因频率和等位基因频率不同,LIPG和MYLIP的基因频率和等位基因频率在正常体重和超重/肥胖者之间也不同(P&lt;0.05~0.001)。正常体重者的TC、ApoA1(ABCA-1);TC、LDLc、ApoA1、ApoB及ApoA1/ApoB(LIPC);TG、HDLc及ApoA1(LIPG);TC、HDLc、LdLc、ApoA1及ApoB(MTHFR);高密度脂蛋白胆固醇及ApoA1(MYLIP)在不同基因型之间存在差异(P&lt0.01~0.001)。超重/肥胖人群的低密度脂蛋白、载脂蛋白B及载脂蛋白A1/载脂蛋白B(ABCA-1);高密度脂蛋白-C、载脂蛋白A1、载脂蛋白B及载脂蛋白A1/载脂蛋白B(LIPC);总胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1及载脂蛋白B(LIPG);总胆固醇、甘油三酯、高密度脂蛋白-C、低密度脂蛋白-C、载脂蛋白A1及载脂蛋白B(MTHFR);总胆固醇、甘油三酯及载脂蛋白B(MYLIP);甘油三酯(PCSK9);甘油三酯(TG)、载脂蛋白A1(ApoA1)及载脂蛋白B(ApoB)(PPARD);以及总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白-C、载脂蛋白A1及载脂蛋白B(SCARB1)在超重/肥胖人群中存在差异(P<0.01;-0.001)。ABCA-1(低密度脂蛋白和载脂蛋白A1/载脂蛋白B);低密度脂蛋白胆固醇(TC、LDL-C、ApoA1和ApoB);LIPG(载脂蛋白B);MTHFR(总胆固醇、甘油三酯和低密度脂蛋白);MYLIP(TC和TG);PCSK9(甘油三酯、高密度脂蛋白、载脂蛋白B和载脂蛋白A1/载脂蛋白B);PPARD(甘油三酯和载脂蛋白A1/载脂蛋白B);和SCARB1(甘油三酯、载脂蛋白A1和载脂蛋白B)与超重/肥胖相互作用影响血脂水平(P&lt0.05-0.001)。正常体重和超重/肥胖者之间血脂水平的差异可能部分是由于不同的基因多态性以及几个SNPs与超重/肥胖者之间的交互作用所致。
Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24–28, and > 28 kg/m2; respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001). The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity.
DOI: 10.1001/jama.2009.2014
发表时间: 2010-01-20
影响因子: 120.7
作者:
Flegal, Katherine M.;Carroll, Margaret D.;Curtin, Lester R.
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DOI: 10.1210/jc.2009-1465
发表时间: 2010-03-01
影响因子: 5.8
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发表时间: 2011-06-01
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通讯作者: De Courcy, Genevieve Potier
DOI: 10.1038/ng.291
发表时间: 2009-01
期刊: Nature genetics
影响因子: 30.8
作者:
Kathiresan S;Willer CJ;Peloso GM;Demissie S;Musunuru K;Schadt EE;Kaplan L;Bennett D;Li Y;Tanaka T;Voight BF;Bonnycastle LL;Jackson AU;Crawford G;Surti A;Guiducci C;Burtt NP;Parish S;Clarke R;Zelenika D;Kubalanza KA;Morken MA;Scott LJ;Stringham HM;Galan P;Swift AJ;Kuusisto J;Bergman RN;Sundvall J;Laakso M;Ferrucci L;Scheet P;Sanna S;Uda M;Yang Q;Lunetta KL;Dupuis J;de Bakker PI;O'Donnell CJ;Chambers JC;Kooner JS;Hercberg S;Meneton P;Lakatta EG;Scuteri A;Schlessinger D;Tuomilehto J;Collins FS;Groop L;Altshuler D;Collins R;Lathrop GM;Melander O;Salomaa V;Peltonen L;Orho-Melander M;Ordovas JM;Boehnke M;Abecasis GR;Mohlke KL;Cupples LA
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发表时间: 1996-04-01
期刊: Journal of cardiovascular risk
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通讯作者: Austin, M A