The chromosomal localization of apM-1 was investigated by FISH and mapped to human chromosome 1q21.3-1q23, a region that was identified as a susceptibility locus for Familial Combined Hyperlipidaemia (FCH) and polygenic NIDDM.
Prospective longitudinal studies revealed that the plasma levels of adiponectindeclined at an early phase of obesity and remained decreased after the development of type 2 diabetes.
Genome-wide scans have mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located.
Although family-based association analysis with T2D did not reach significance, our results suggest that an at-risk haplotype of common variants located in the promoter and rare mutations in exon 3 contribute to the variation of the adipocyte-secreted adiponectin hormone level, and may be part of the genetic determinants for T2D in the French Caucasian population.
Based on these findings together with the observation that adiponectin improves insulin sensitivity in animal models, we conclude that the adiponectin gene may be a susceptibility gene for type 2 diabetes.
Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians.
However, adiponectin plasma concentrations are low in obese subjects, and hypoadiponectinemia is associated with the metabolic syndrome, which is a cluster of insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia.
Linkage was also present after inclusion of adiponectin concentrations of siblings with type 2 diabetes not treated pharmacologically (total siblings 582, 182 families, 860 sib-pairs: LOD = 3.5).
Low levels of adiponectin are associated with low levels of HDL-cholesterol independently from common metabolic risk factors and therefore represent an independent cardiovascular risk factor in type 2 diabetes.
The complex aetiology of Type 2 diabetes, which probably involves a medley of molecular mechanisms, requires dissection out of diabetes-associated subphenotypes, such as the non-obese with increased liver fat or the obese with low plasma adiponectin.
This result indicated that the type 2 diabetes susceptibility locus at 3q27 influences both genetic predisposition to type 2 diabetes and serum adiponectin levels in patients with type 2 diabetes.
We have reported that adiponectin has antiatherogenic and antidiabetic properties, and that the plasma levels negatively correlated with body mass index (BMI) are significantly low in patients with CAD or type 2 diabetes.
However, first-degree relatives of subjects with type 2 diabetes and those without a family history of diabetes had normal and comparable levels of CRP, adiponectin, and complement proteins.
The present study provides additional evidence that SNPs in the proximal promoter region of the APM1 gene contribute to the development of type 2 diabetes.
Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies.