Cesari Maurizio, Narkiewicz Krzysztof, De Toni Renzo, Aldighieri Enrico, Williams Christopher J, Rossi Gian Paolo
Department of Clinical and Experimental Medicine, Clinica Medica 4 University Hospital, University of Padova, Italy.
J Clin Endocrinol Metab. 2007 Aug;92(8):3082-8. doi: 10.1210/jc.2007-0403. Epub 2007 May 29.
Adiponectin is suspected to exert antiatherogenic, antiinflammatory, and insulin-sensitizing effects. However, the relative importance of the genetic and environmental factors in influencing plasma adiponectin levels (ADPN) remains unclear.
The aim of the study was to investigate whether ADPN and body mass index (BMI) are genetically determined.
DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES: In a series of 60 pairs of healthy twins, we estimated genetic variance and heritability of ADPN and BMI using both ANOVA and path analysis methods. Twins were genotyped at two biallelic single nucleotide polymorphisms (SNPs) at the gene encoding adiponectin: the +45 T/G (on exon 2) and the -11377 G/C (on the promoter).
A total of 30 pairs of twins were Monozygotic (MZ), and 30 were dizygotic (DZ). The mean ADPN (+/-SD) was 10.6 +/- 5.7 in MZ and 11.1 +/- 4.5 in DZ twins (nonsignificant). Three tests of heritability (within pair = 1.13, P < 0.0001; among components = 1.62, P = 0.005; and intraclass correlation 1.34, P < 0.0001) consistently showed ADPN heritability. The preferred model of a likelihood-based analysis included an additive genetic influence and an individually unique environmental influence for ADPN, accounting for 88% and 12% of ADPN variance, respectively. We found a significantly higher within-pair difference of ADPN in DZ than in MZ pairs, and in +45 T/G SNP discordant compared with concordant DZ twins, indicating a significant effect of this adiponectin gene SNP on ADPN.
ADPN shows significant genetic variance and heritability, which is independent of BMI and partly accounted for by the +45 T/G, but not the -11377 G/C adiponectin gene SNP.
脂联素被怀疑具有抗动脉粥样硬化、抗炎和胰岛素增敏作用。然而,遗传和环境因素在影响血浆脂联素水平(ADPN)方面的相对重要性仍不清楚。
本研究旨在调查ADPN和体重指数(BMI)是否由基因决定。
设计、地点、参与者和主要观察指标:在一系列60对健康双胞胎中,我们使用方差分析和路径分析方法估计了ADPN和BMI的遗传方差和遗传力。对双胞胎在脂联素编码基因的两个双等位基因单核苷酸多态性(SNP)处进行基因分型:+45 T/G(位于外显子2)和-11377 G/C(位于启动子)。
共有30对双胞胎为同卵双胞胎(MZ),30对为异卵双胞胎(DZ)。MZ双胞胎的平均ADPN(±标准差)为10.6±5.7,DZ双胞胎为11.1±4.5(无显著性差异)。三项遗传力测试(配对内=1.13,P<0.0001;成分间=1.62,P=0.005;组内相关系数1.34,P<0.0001)一致显示ADPN具有遗传力。基于似然性分析的首选模型包括ADPN的加性遗传影响和个体独特的环境影响,分别占ADPN方差的88%和12%。我们发现DZ双胞胎中ADPN的配对内差异显著高于MZ双胞胎,并且在+45 T/G SNP不一致的DZ双胞胎中与一致的DZ双胞胎相比差异显著,表明该脂联素基因SNP对ADPN有显著影响。
ADPN显示出显著的遗传方差和遗传力,其独立于BMI,部分由+45 T/G而非-11377 G/C脂联素基因SNP所解释。