脂联素启动子基因多态性与2型糖尿病及并发症的相关性研究

目的 观察脂联素(APN)启动子基因单核苷酸多态性(SNP)频率与2型糖尿病(T2DM)及其合并症间的相关性,探讨脂联素基因(aPM1)突变是否是T2DM遗传的危险因素.并确立一种高效、准确、经济的检测APN基因实用筛查方法,供临床检测应用.方法 对单纯T2DM49例(男28例,女21例)、T2DM合并高血压(T2DM-HP)90例(男51例,女39例)、T2DM合并冠心病(T2DM-CHD)33例(男15例,女18例)、T2DM合并肾病(T2DM-NE)41例(男18例,女23例)患者和健康对照组58名(男30名,女28名),测定空腹血清生化指标.采用变性高效液相色谱(DHPLC)技术,筛选APN基因多态性位点.结果 在APN基因(aPM1)启动子区扩增的片段与基因库中登陆的APN GeneID:9370序列相比,存在点突变(-11377G/C).GG、GC、CC基因频率在T2DM组和对照组分别为:5.16%、42.25%、52.58%和3.40%、32.75%、63.85%.T2DM患者aPM1 的SNP-11377位点G等位基因频率明显高于健康对照组(x2=6.818,OR=0.55,P=0.033).从T2DM基因型分组临床资料比较可见,-11377G/C基因型与T2DM患者的收缩压(P=0.035)、体重指数(BMI)(P=0.010)、腹围(P=0.013)和腰臀比(P=0.015)显著相关.通过对试验条件优化,在采用DHPLC技术检测APN基因多态性位点发现,本试验检测柱温以60℃最佳.结论 aPM1启动子区SNP-11377C/G多态性与T2DM及并发症的发生和T2DM患者体型肥胖形成机制有相关性,提示SNP.11377C/G多态性可能增加T2DM的遗传风险.     

脂联素基因突变-11377C/G检测方法建立及与2型糖尿病关系的研究

目的建立脂联素基因（aPM1）-11377C/G点突变的检测方法,探讨aPM1-11377C/G点突变单核苷酸多态性（SNP）与血清脂联素（APN）水平及2型糖尿病（T2DM）的相关性。方法构建含aPM1-11377C/G点突变的野生型和突变型质粒标准品,采用等位基因特异性PCR（ARMS-PCR）方法,结合荧光探针（TaqMan Prob）,通过对引物3′端正配与错配扩增效率差别的比较,建立ARMS-TaqMan检测aPM1-11377C/G点突变的方法。同时,分别对156例（男87/女69）糖尿病患者（T2DM组）和89例（男21/女68）健康对照者（NC组）的aPM1-11377C/G基因频率,以及APN、各种生化指标以及临床基本资料进行检测和调查。结果 T2DM组APN水平显著低于NC组（P〈0.05）。aPM1-11377位点CC、CG、GG基因的APN水平呈趋势性降低（P〈0.001）。T2DM组与对照组间的aPM1-11377位点CC、CG、GG基因频率差异有显著性（P〈0.05）。T2DM组的aPM1-11377 G等位基因频率显著高于NC组（24.36%vs.19.11%,P〉0.05）。结论 ARMS-TaqMan方法检测aPM1-11377C/G基因点突变具有准确、经济和适合高通量检测的特点。aPM1-11377C/G多态性与血清脂联素水平和T2DM相关。     

脂联素及其基因多态性与广西地区壮族代谢综合征患者的相关性

目的探讨脂联素(APN)及其基因位点+45 T/G和-11377 C/G的多态性与广西地区壮族代谢综合征(MS)患者的相关性。方法 ELISA法检测广西地区壮族和汉族MS患者、壮族和汉族健康人群(各100例)血清APN水平,PCR-RFLP技术检测APN基因-11377 C/G和+45 T/G位点多态性。结果与同民族健康组比较,两民族MS组血清APN水平均降低(P均0.05)。4组受试者APN+45等位基因分布频率差异有统计学意义(χ~2=26.560,P=0.000),且与同民族健康对照组比较TT和TG基因型分布频率降低,GG基因型升高(P均0.05)。4组受试者APN-11377位点等位基因分布频率差异无统计学意义(χ~2=2.051,P=0.562)。此外,不同民族MS患者APN+45 T/G基因型间血清APN水平差异有统计学意义,且与同民族TT基因型比较,TG和GG型均降低(P均0.05)。结论 APN+45位点的多态性及血清APN水平改变可能与广西地区壮族和汉族MS发生密切相关。     

脂联素及其基因多态性与广西瑶族冠心病的关系

目的 探讨广西地区瑶族冠心病患者血清中脂联素(APN)水平及其基因位点+276 G/T和-11377 C/G的多态性。方法 瑶族、汉族冠心病患者、瑶族和汉族正常人各100例纳入研究。采用酶联免疫吸附法(ELISA)检测研究对象血清中APN水平,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测APN基因位点+276G/T和-11377C/G的多态性。结果 ①两组冠心病组血清中APN水平明显低于两组正常组,差异有统计学意义(t=10.311,8.642; 均P=0.000)。瑶族冠心病组和汉族冠心病组血清中APN的差异无统计学意义(t=1.792,P=0.076); ②在H-W平衡检验中,四组中APN基因位点+276G/T和-11377C/G均具有群体代表性(均P＞0.05); ③四组APN+276G/T位点的主要型别是野生型。4组间APN+276G/T位点的等位基因频率均无显著差异(均P＞0.05); ④冠心病组ANP-11377C/G基因型和等位基因频率与同民族正常组的差异有统计学意义(χ²=8.908,P=0.012; χ²=17.275,P=0.000); 瑶族冠心病组APN-11377C/G基因杂合程度略低于汉族冠心病组,但差异无统计学意义(χ²=0.363,P=0.834)。结论 同汉族冠心病一样, 血清低APN水平和APN-11377C/G位点是瑶族冠心病患者的危险因素。     

脂联素及其基因多态性与某地冠心病的相关性研究

目的探讨某地瑶族冠心病(CHD)患者血清脂联素(APN)水平及其基因位点+45T/G和-11377C/G的多态性与该地区瑶族健康者、汉族CHD患者、汉族健康者的差异。方法采用酶联免疫吸附(ELISA)方法检测瑶族CHD患者、瑶族健康者、汉族CHD患者和汉族健康者(各100例)血清APN水平;使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测APN基因位点+45T/G和-11377C/G的多态性。结果 (1)2组CHD患者血清APN水平明显低于2组健康对照者,差异有统计学意义(均P0.05)。2组CHD患者血清APN水平差异无统计学意义(P=0.076)。(2)在H-W平衡检验中,4组研究对象APN基因位点+45T/G和-11377C/G均有群体代表性(均P0.05)。(3)瑶族CHD患者ANP+45TG、GG基因型频率均高于瑶族健康者,但差异无统计学意义(P0.05);汉族CHD患者ANP+45基因型等位基因频率略高于瑶族CHD患者,但差异无统计学意义(P0.05)。(4)CHD患者ANP-11377基因型和等位基因频率与同民族健康者比较,差异有统计学意义(P0.05);瑶族CHD患者APN-11377基因杂合程度略低于汉族CHD患者,但差异无统计学意义(P0.05)。结论血清低APN水平和APN-11377位点是瑶族CHD患者的危险因素,与汉族CHD患者相同。     

脂联素基因SNPs-11377C/G多态性与女性乳腺癌的相关性

目的探讨脂联素基因SNPs-11377C/G多态性与女性乳腺癌发生的相关性。方法用聚合酶链式反应-限制性内切酶长度多态性(PCR-RFLP)技术观察脂联素基因在不同人群中的单核苷酸多态性,其中包括乳腺癌组患者70人,健康对照组30人。结果 SNPs-11377C/G等位基因频率在乳腺癌和正常对照组间分布差异无统计学意义(P0.05),乳腺癌患者组CG基因型分布频率高于GG型和对照组相比差异有统计学意义(P0.05)。乳腺癌组CC基因型CA153与CEA表达水平高于对照组(P0.05),差异有统计学意义。结论脂联素基因启动子区SNPs-11377C/G基因多态性与乳腺癌疾病发生有相关性。     

中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病易感性的Meta 分析

目的 探讨中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病易感的相关性.方法 检索2011年11月前中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、万方数据库、维普中文科技期刊数据库(VIP)及Medline、Cochrane Library、Embase、Springer、Ovid等数据库,收集有关中国人群脂联素基因-11377C/G多态性与2型糖尿病的相关性研究;评价纳入研究质量,提取有效数据,采用Review Manager5.0软件进行Meta分析.结果 共纳入12组研究中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病的相关性的病例-对照研究,2型糖尿病病例2 598例,对照4 508例.Meta分析发现,脂联素基因启动子区-11377C/G位点C/G多态性与2型糖尿病相关性中G等位基因与C等位基因[OR=1.14,95%CI(1.03,1.25),P=0.009]、基因型(CG+GG)与CC[OR=1.19,95%CI(1.06,1.35),P=0.004]、基因型CG与CC[OR=1.14,95%CI(1.00,1.29),P=0.05]、基因型GG与CC[OR=1.34,95%CI(1.06,1.71),P=0.02]均具有统计学意义差异.结论 中国人群脂联素基因启动子区-11377C/G位点多态性与2型糖尿病易感性存在相关性.     

脂联素基因启动子区-11377C／G单核苷酸多态性与中国北方汉族人2型糖尿病的关系

目的:分析脂联素基因启动子区-11377C/G(SNPs-11377C/G)单核苷酸多态性与中国北方汉族人2型糖尿病的关系。方法:选择2004/2005北京市和黑龙江哈尔滨地区的2型糖尿病流行病学调查资料中有糖尿病家族史,且相互间无亲缘关系的2型糖尿病患者348例,同时选择非糖尿病健康对照378例。所有研究对象均为汉族人,均签署了知情同意书。用聚合酶链反应-限制性片段长度多态方法鉴定脂联素基因启动子区SNPs-11377C/G的单核苷酸多态性。结果:726例研究对象均进入结果分析。①2型糖尿病组中CC,CG,GG基因型分别为171例(49.1%),151例(43.4%),26例(7.5%),正常对照组中CC,CG,GG基因型分别为180例(47.6%),173例(45.8%),25例(6.6%)。SNPs-11377C/G的基因型频率和等位基因频率在2型糖尿病组和正常对照组中的分布差异无显著性(P>0.05)。②SNPs-11377C/G的基因型频率和等位基因频率的分布性别差异也无显著性(P>0.05)。③SNPs-11377C/G不同基因型组中肥胖指标(体质量指数、腰围和腰臀比)的特征差异也无显著性(P>0.05)。结论:脂联素基因启动子区-11377C/G(rs266729)单核苷酸多态性与中国北方汉族人2型糖尿病无明显相关性。     

云南汉族脂联素基因-11377 C＞G多态性特点

目的:研究脂联素基因-11377 C＞G在云南汉族人群中的基因多态性特点.方法:应用MassArray分子量阵列技术,对83例云南汉族人群脂联素基因-11377 C＞G单核苷酸多态性进行检测.结果:云南汉族人群中脂联素基因-11377 C＞G的CC、CG、GG基因型频率分别为46.4％、48.8％和4.8％,C、G等位基因频率分别为70.8％和29.2％. CC基因频率和C等位基因频率与国内各研究、日本人、多数高加索人间无显著性差异(p＞0.05),但明显低于南非黑人,差异存在统计学意义(p＜0.001),明显高于瑞典人群(p＜0.001).结论:不同人种间-11 377 C＞G是存在种族差异性的.     

脂联素基因rs2241766 多态性与代谢综合征的相关性研究

目的 探讨脂联素(adiponectin,APN)rs2241766基因多态性与代谢综合征(metabolic syndrome,MS)患者发生的关系。方法 410例MS患者和203例健康人群纳入研究。使用酶联免疫吸附试验(ELISA)检测研究对象的血清APN水平,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测APN基因rs2241766 位点T/G基因的多态性,分析各基因型与MS发生的关系。结果 MS患者血清APN水平明显低于对照组(15.3 ± 4.4 mg/ml vs 27.2 ± 6.5 mg/ml),差异有统计学意义(χ²=41.7,P< 0.001); rs2241766位点三种基因型在MS组与对照组间的分布,差异有统计学意义(χ²=39.222,P< 0.001),MS组G等位基因频率高于健康人群,差异有统计学意义(χ²=36.657,P< 0.001); logistic回归分析显示研究组G等位基因发生MS的风险高于T等位基因(OR=2.19, 95% CI:1.17～3.01 vs OR=1.00ref),差异有统计学意义(P=0.034,<0.05)。TG和GG基因型发生MS的风险较TT基因型增高(OR=1.55, 95% CI:0.79～2.83; OR=2.48, 95% CI:1.67～7.35 vs OR=1.00ref),将TG和GG基因型合并后发生MS风险同样增高(OR=2.23,95% CI:1.21～6.09),差异均有统计学意义(P=0.019,0.006,0.029),且TG(15.7± 4.1 mg/ml)及GG(14.3 ± 4.5 mg/ml)基因型研究对象的APN水平低于TT基因型(18.7± 4.9 mg/ml),差异有统计学意义(F=7.621,P< 0.001)。结论 MS的发生可能与rs2241766位点的基因变异相关,尤其是T向G变异的个体发生MS的风险更高,使APN水平降低。     

脂联素基因多态性与肥胖、血清脂联素水平的相关性

目的：研究发现，脂肪组织分泌的脂联素在体脂变化，糖、脂代谢以及抗动脉粥样硬化中发挥有益的作用。分析脂联素基因（apMl）多态性与肥胖、血清脂联素水平的相关性。 方法：（1）试验对象：选取2000-08／2003-07在上海市华阳社区肥胖流行病学调查所诊断的超重，月巴胖人群以及上海市第六人民医院门诊就诊的390名患者。男171例，女219例，平均年龄（51±1）岁。纳入标准：①符合世界卫生组织（WHO）肥胖诊断标准。②所有纳入对象均为汉族人。③对试验目的知情同意。（2）试验方法及评估：根据世界卫生组织（WHO）肥胖诊断标准将受试对象分为正常体质量组（体质量指数〈25kg／m^2）182例和超重，月巴胖组（≥25kg／m^2）208例。进一步根据腹腔内脂肪面积将超重，月巴胖组分为腹内型肥胖（腹腔内脂肪面积≥100cm^2）114例和非腹内型肥胖（腹腔内脂肪面积〈100cm^2）94例。采用多聚酶链反应一限制性片段长度多态性方法检测apM1基因第二外显子＋45（Exon2＋45）和第三外显子＋331（Exon3＋331）2个位点的基因多态性。应用核磁共振测定局部体脂，放射免疫分析法测定空腹血清脂联素水平。试验对数据先进行正态分布检验，如果符合正态分布，两组间计量资料的比较采用t检验，多组间比较用啦验。计算基因多态性的基因型频率，确认符合Hardy-Weinberg平衡，计算等位基因频率，基因型分布作Hardy-Weinberg吻合度检验。等位基因频率和基因型频率的比较采用x。检验。 结果：正常对照组182例和超重，月巴胖组208例均进入结果分析。①中国汉族人apMl基因Exon2＋45位点存在基因多态性，有3种基因型，即TT，TG，GG；Exon3＋331位点不存在基因多态性，均为TT基因型。②apMl基因Exon2＋45位点基因型及等位基因频率在超重，月巴胖者与正常体质量者之间无?     

脂联素基因多态性与肥胖、血清脂联素水平的相关性

目的:研究发现,脂肪组织分泌的脂联素在体脂变化,糖、脂代谢以及抗动脉粥样硬化中发挥有益的作用.分析脂联素基因(apM1)多态性与肥胖、血清脂联素水平的相关性.方法:⑴试验对象:选取2000-08/2003-07在上海市华阳社区肥胖流行病学调查所诊断的超重/肥胖人群以及上海市第六人民医院门诊就诊的390名患者.男171例,女219例,平均年龄(51±1)岁.纳入标准:①符合世界卫生组织(WHO)肥胖诊断标准.②所有纳入对象均为汉族人.③对试验目的知情同意.⑵试验方法及评估:根据世界卫生组织(WHO)肥胖诊断标准将受试对象分为正常体质量组(体质量指数＜ 25 kg/m2)182例和超重/肥胖组(≥25 kg/m2)208例.进一步根据腹腔内脂肪面积将超重/肥胖组分为腹内型肥胖(腹腔内脂肪面积≥100 cm2)114例和非腹内型肥胖(腹腔内脂肪面积＜100 cm2)94例.采用多聚酶链反应-限制性片段长度多态性方法检测apM1基因第二外显子 45(Exon2 45)和第三外显子 331(Exon3 331)2个位点的基因多态性.应用核磁共振测定局部体脂,放射免疫分析法测定空腹血清脂联素水平.试验对数据先进行正态分布检验,如果符合正态分布,两组间计量资料的比较采用t检验,多组间比较用F检验.计算基因多态性的基因型频率,确认符合Hardy-Weinberg平衡,计算等位基因频率,基因型分布作Hardy-Weinberg吻合度检验.等位基因频率和基因型频率的比较采用χ2检验.结果:正常对照组182例和超重/肥胖组208例均进入结果分析.①中国汉族人apM1基因Exon2 45位点存在基因多态性,有3种基因型,即TT,TG,GG;Exon3 331位点不存在基因多态性,均为TT基因型.②apM1基因Exon2 45位点基因型及等位基因频率在超重/肥胖者与正常体质量者之间无显著差异;在腹内型肥胖与非腹内型肥胖者间亦无显著差异.③apM1基因Exon2 45位点各基因型组间血清脂联素水平无显著差异.结论:中国汉族人脂联素基因Exon2 45位点的多态性与肥胖以及肥胖类型、血清脂联素水平无相关性;Exon3 331位点不存在基因多态性.     

Improved ELISA for selective measurement of adiponectin multimers and identification of adiponectin in human cerebrospinal fluid

BACKGROUND: Human serum adiponectin exists in 3 multimer forms: high molecular weight (HMW), middle molecular weight, and low molecular weight (LMW), with some of the latter bound to albumin (Alb)-LMW. Some studies have suggested that adiponectin crosses the blood-brain barrier and plays a central role in energy homeostasis. METHODS: To determine cerebrospinal fluid (CSF) adiponectin at extremely low concentrations, we modified the protocol of the ELISA system used to assay serum adiponectin. The 3 multimers of adiponectin were measured separately by pretreating CSF with 2 proteases. We measured the CSF adiponectin concentrations in anonymous human samples (n = 19). The molecular sizes of adiponectin in CSF pretreated with proteases or untreated were determined by use of native PAGE and immunoblotting. RESULTS: The ELISA system measured adiponectin in the range of 1.0-167 microg/L. The between-assay imprecision estimates (CVs) were 6%-17% for the 3 forms. The mean total CSF adiponectin concentration (7.2 microg/L) was approximately 1/1000 of the mean concentration in serum. Unlike serum adiponectin, the LMW and Alb-LMW forms predominated in all of the CSF samples. Immunoblotting analysis revealed that most LMW forms were bound to Alb, although the HMW form was detected in some samples. CONCLUSIONS: The modified ELISA system measures the 3 multimers separately and is sufficiently sensitive to measure adiponectin in CSF.     

血清脂联素水平与高血压的关系

目的探讨血清脂联素水平与高血压的关系。方法根据JNC-7的血压标准,筛选出30例高血压患者,年龄35～72岁,平均（53．78±9．29）岁。并筛选出同期在我院体检中心观察的健康人30例,年龄34～70岁,平均（52．00±10．33）岁。所有入选者清晨空腹抽取外周静脉血,用酶联免疫法测定血清脂联素水平。结果与正常对照组相比,高血压组血清脂联素水平明显降低（4．21±2．89ng／ml VS2．69±1．0ng／m1）。t检验表明两组之间差异具有显著性（P〈0．01）。结论高血压患者血清脂联素水平明显降低,低水平的脂联素血症在高血压发病中可能起重要作用。     

Biovariability of plasma adiponectin.

BACKGROUND: Adiponectin is a cytokine produced by adipose tissue with insulin sensitising and anti-atherosclerotic effects. Low plasma adiponectin levels are used as a marker of the metabolic syndrome and incipient type 2 diabetes. METHODS: We carried out a series of studies to determine the short- and long-term variability of plasma adiponectin levels, including diurnal and post-prandial changes. These investigations also included examining the effect of frozen storage on plasma adiponectin levels. RESULTS: A nested study in 10 overweight subjects with the metabolic syndrome and 10 age- and sex-matched controls showed intra-subject variation in adiponectin levels over a 30-day period of 12.2% and 18.8%, respectively, equivalent to reference change values of 1.7 and 3.6 microg/mL. In non-obese subjects, plasma adiponectin levels varied minimally over a 15-month period (baseline, 8.3+/-2.9 microg/mL vs. +15 months, 8.2+/-3.0 microg/mL, p=0.95) and showed only minor diurnal and post-prandial changes (pre-meal, 8.2+/-3.0 microg/mL vs. 3 h post-prandial, 8.3+/-3.1 microg/mL, p=0.60). The adiponectin assay had an intra-assay variation of 8.8%, with storage at -30 degrees C for 33 months or three cycles of freezing and thawing having no discernible effect on adiponectin levels. CONCLUSIONS: These results demonstrate that plasma adiponectin levels have relatively low biovariability and that adiponectin can be sampled fasting or non-fasting to provide a reliable marker of insulin resistance and incipient type 2 diabetes.     

脂联素在动脉硬化中的保护作用

脂联素(adiponectin)是一种脂肪组织特异性细胞因子,体外研究发现在受损伤的血管壁上存在脂联素的浓集。细胞培养证实脂联素具有抑制造血细胞分化的功能,可抑制巨噬细胞的吞噬活性及向泡沫细胞的转化;抑制血管内皮细胞及平滑肌细胞(SMC)的增殖、分化及向内皮下损伤区的迁移。而内皮细胞、巨噬细胞和SMC正是构成动脉粥样硬化灶的三要素。动物在体研究发现脂联素基因缺陷小鼠(adipo-/-)体内动脉内膜明显增厚。临床研究发现,正常人血循环中含有丰富的脂联素蛋白,而在肥胖、糖尿病及冠心病患者体内脂联素表达水平显著降低,是冠心病发病的独立危险因素。种种迹象表明脂联素在动脉粥样硬化的发生发展中扮演着一定的保护性角色。     

Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans

Low adiponectin levels are an independent risk factor for and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then used KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue, but the expression of AdipoRs is not statistically different from nonneoplastic tissues. We also show for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1, which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion, and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer.     

Linking adiponectin to proteinuria

Obesity predisposes toward renal disease independently of diabetes and hypertension. In this issue of the JCI, Sharma and colleagues assessed the role of adiponectin, an adipose-derived hormone, in the pathogenesis of albuminuria (see the related article beginning on page 1645). Obese African Americans had reduced adiponectin levels associated with albuminuria. Adiponectin deficiency in mice induced oxidative stress, fusion of podocyte foot processes in the kidney glomerulus, and urinary albumin excretion. Adiponectin treatment reversed these abnormalities, likely through activation of AMPK. The benefits of adiponectin were observed in diabetic and nondiabetic mice. These findings suggest that adiponectin is a biomarker for kidney disease and may be targeted for prevention and treatment.     

The influence of the adiponectin gene on adiponectin concentrations and parameters of metabolic syndrome in non-diabetic Korean women

BACKGROUND: Concentrations of adiponectin, the protein product of the adipocyte C1q and collagen-domain-containing (ADIPOQ) gene are associated with type 2 diabetes and coronary artery disease. We investigate the association of single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene with adiponectin concentrations, and to parameters of metabolic syndrome. METHODS: 867 unrelated, non-diabetic Korean women, 20 to 69 y, were genotyped for 8 SNPs in the ADIPOQ gene (-11391G>A, -11377C>G, H241P, Y111H, G90S, R221S, 45T>G, 276G>T). Adiponectin, a homeostasis model assessment of insulin resistance (HOMA-IR), and metabolic parameters were measured. RESULTS: Carriers of genotype T/T at position 276 had significantly higher adiponectin concentrations than G/G carriers (P=0.005). Homozygous carriers of the TG haplotype (i.e., individuals who were T/T at 45 and G/G at 276) and heterozygous carriers of the TG haplotype (TG/X) had lower adiponectin concentrations than non-TG carriers (P<0.001). Significant associations between SNP at 276 and serum concentrations of triglyceride (P=0.013), insulin (P=0.013) and HOMA-IR (P=0.012) were found. The 45-276 haplotypes had associations identical to the 276G>T SNP. In subgroup analysis, subjects carrying the TG haplotype had significantly lower adiponectin concentrations than non-TG carriers in both normal weight (P<0.001) and overweight-obese (P=0.009) subgroups. The association of the TG haplotype with increasing insulin concentrations was significant among overweight-obese subjects (P=0.004), but was not significant among normal weight subjects. A similar association was found between the 45-276 haplotype and HOMA-IR. CONCLUSION: There is a strong association of the adiponectin SNP276 genotypes and the adiponectin 45-276 haplotypes with circulating adiponectin concentrations in non-diabetic Korean women. In addition, this haplotype is associated with increased insulin concentrations and insulin resistance index only in overweight-obese individuals.