title: The SNP276G>T polymorphism in the adiponectin (ACDC) gene is more strongly associated with insulin resistance and cardiovascular disease risk than SNP45T>G in nonobese/nondiabetic Korean men independent of abdominal adiposity and circulating plasma adiponectin.
abstract: This study aimed to determine whether polymorphisms of the adiponectin (ACDC) gene independently contribute to insulin resistance (IR) and other cardiovascular disease (CVD) risk factors in nonobese, nondiabetic Korean men after adjusting for major environmental factors that influence IR. Among the 7 ACDC single-nucleotide polymorphisms (SNPs;C-11377G, T45G, G276T, H241P, Y111H, G90S, and R221S) prescreened in 48 subjects, we genotyped 333 subjects for SNP45 and SNP276, both of which showed an allele frequency of more than 2%. In Pearson correlation and multiple stepwise regression analyses, we found that waist circumference was the most important influencing factor (beta = .369, P < .001) in homeostasis model assessment (HOMA)-IR, whereas plasma adiponectin was the second most important (beta = -.217, P = .023). At position 276, T/T subjects showed significantly lower glucose concentrations (P = .043) and higher low-density lipoprotein particle sizes (P = .033) than the G/G and G/T subjects. The subjects also had lower serum triglycerides and HOMA-IR; however, these results were not statistically significant. After adjusting for waist circumference and plasma adiponectin, T/T subjects showed a significantly lower HOMA-IR than G/G or G/T subjects (P = .048). On the other hand, at position 45, only glucose concentrations were significantly lower in G carriers (P = .005). In the SNP45-SNP276 haplotype test, TT/TT subjects (having T/T at both SNP45 and SNP276) showed significantly lower IR before and after adjusting for waist circumference and adiponectin levels than did other carriers. In conclusion, we suggest that SNP276G>T, rather than SNP45T>G, is more strongly associated (both directly and indirectly) than with several components of metabolic syndrome and CVD risk, including IR, triglyceride concentration, and low-density lipoprotein particle size, in nonobese, nondiabetic men.
authors.affiliation: Division of Cardiology, Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Oh Yoen
authors.initials: OY
authors.lastname: Kim
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Koh
authors.forename: Jey Sook
authors.initials: JS
authors.lastname: Chae
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Woo
authors.forename: Hongkeun
authors.initials: H
authors.lastname: Cho
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D000005:Abdomen / Q000033:anatomy & histology / Q000502:physiology; D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology*; D000328:Adult; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D001827:Body Height / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008054:Lipid Peroxides / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D010316:Particle Size; D011110:Polymorphism, Genetic / Q000502:physiology*; D012307:Risk Factors
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D008054:Lipid Peroxides; D008055:Lipids; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D002097:C-Reactive Protein