Context: Adiponectin is suspected to exert anti-atherogenic, anti-inflammatory and insulin-sensitizing effects. However, the relative importance of the genetic and the environmental factors in influencing plasma adiponectin levels (ADPN) remains unclear.

Objective: to investigate whether ADPN and body mass index are genetically determined.

Design, Setting, Participants and Main Outcome Measure: In a series of 60 pairs of healthy twins, we estimated genetic variance and heritability of ADPN and body mass index using both analyses of variance 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).

Results: 30 pairs of twins were monozygotic (MZ) and 30 were dizygotic (DZ). The mean ADPN (±SD) were 10.6±5.7 in MZ and 11.1±4.5 in DZ twins (NS). Three tests of heritability (within pair=1.13, p<0.0001; among components=1.62, p=0.005; intraclass correlation: 1.34, p<0.0001) consistently showed ADPN heritability. The preferred model of a likelihood-based analysis included an additive genetic influence (A) and an individually unique environmental (E) 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 to concordant DZ twins indicating a significant effect of this adiponectin gene SNP on ADPN.

Conclusions: ADPN shows significant genetic variance and heritability, which is independent on BMI and partly accounted for by the +45 T/G but not the -11377 G/C adiponectin gene SNP.