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From our preliminary results, human zinc-α(2) -glycoprotein may be a novel urinary biomarker for non-albuminuric diabetic nephropathy.

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Accumulating data suggest that bone plays a role in energy metabolism through decarboxylation of osteocalcin. Thus, we aimed to study the association of circulating under--carboxylated osteocalcin (UC-OCN) and car-boxylated osteocalcin (C-OCN) with metabolic syndrome in middle aged Asian population.In this cross-sectional study, 131 middle aged Asian subjects were recruited. Circulating UC-OCN, C-OCN and parameters of metabolic phenotype were measured.Circulating UC-OCN was increased in subjects with metabolic syndrome (8.1±7.2 ng/ml vs. 5.9±4.6 ng/ml, p=0.036). In contrast, C-OCN showed a non-significant trend towards reduction in subjects with metabolic syndrome (3.6±2.2 ng/ml vs. 4.3±1.8 ng/ml, p=0.057). Further analysis revealed that changes in both UC-OCN and C-OCN occurred primarily among females with metabolic syndrome. Interestingly, neither forms of OCN differed significantly between individuals with and without metabolic syndrome in males. Logistic regression revealed that UC-OCN was independently associated with metabolic syndrome after adjusting for multiple covariates. However, association between metabolic syndrome and C-OCN was dependent on gender (i. e., amongst females only) in the fully adjusted regression model.Variation in OCN (including its sub-species) was associated with variation in metabolic parameters amongst Asian adults. Circulating UC-OCN was increased while C-OCN was decreased in treatment-naïve females with metabolic syndrome. Our preliminary observations further supported a potential link between bone and energy metabolism in humans.

Background: Adiponectin is the most abundant circulating adipokine in human that regulates insulin actions. Association of adiponectin gene variations with type 2 diabetes (T2DM) has been reported albeit predominantly in non-Asian populations. Additionally, proof of variant functionality beyond statistical association is often unavailable. We studied six common (minor allele frequency ≥0.05) adiponectin single nucleotide polymorphisms (SNPs) in Singaporean Chinese adults with follow-up functional genetic experiments. Methods:In a case-control study (N=588), genotyping of six common adiponectin haplotype tagging SNPs [-3964A>G(rs822396), +45T>G(rs2241766), 276C>A(rs1501299), 973G>A(rs3774262), 4551G>C(rs1063539) and 5852G>A(rs6444175)] was performed using Taqman genotyping assay. Allele-dependent differential efficiency of mRNA expression was tested with quantitative real time PCR using human subcutaneous and omental adipose tissues.Results: Distributions of genotypes for all SNPs among controls were consistent with Hardy-Weinberg Equilibrium. Single locus, genotyped-based analysis suggested borderline significant (P=0.07) association between an exon-2 coding-synonymous +45T>G(rs2241766) and T2DM. We demonstrated that the relative mRNA expression of adiponectin gene was ~80% lower among carriers of minor G allele in human subcutaneous adipose tissue (N=43, p<0.001). The observed allele-dependent differential expression was replicated (~50% reduction) in an independent sample of human omental adipose tissue (N=52, p<0.005).Conclusions: Our data was indicative of possible association between +45T>G(rs2241766) and T2DM among Singaporean Chinese adults. Functional experiments in both human subcutaneous and omental adipose tissue suggested that polymorphisms in +45T>G(rs2241766) may be associated with differential allelic expression. J ou rna l o f D ia be tes & M e ta bolism