Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes. Materials and Methods: We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined. Results: Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02). Conclusion: These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.
Abstract
Purpose: Although some CDH13 single nucleotide polymorphisms (SNPs) have been shown to be determinants of blood adiponectin levels, the clinical implications of CDH13 variants are not yet completely understood. The purpose of this study was to evaluate the effects of SNPs of CDH13 on metabolic and vascular phenotypes. Materials and Methods: We included 238 hypertensive subjects and 260 age- and sex-matched controls. Seven tagging-SNPs were identified in the CDH13 gene by whole gene sequencing. The association between these SNP variants and the risk of hypertension, metabolic traits, and carotid intima-media thickness (IMT) was examined. Results: Minor allele carriers of rs12444338 had a lower risk of hypertension, but the association turned out just marginal after adjusting confoudners. Blood glucose levels were higher in the minor allele carriers of c.1407C>T (p=0.01), whereas low-density lipoprotein-cholesterol levels were greater in those of rs6565105 (p=0.02). The minor allele of rs1048612 was associated with a higher body mass index (p=0.01). In addition, the mean carotid IMT was significantly associated with rs12444338 (p=0.02) and rs1048612 (p=0.02). Conclusion: These results provide evidence that CDH13 variants are associated with metabolic traits and carotid atherosclerosis in Koreans. This study shows the multifaceted effects of CDH13 variants on cardiometabolic risk.
참고문헌 (21)
- Hug C, "T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30", adiponectin, 2004, pp.101, 10308~10313
- Takeuchi T, "Adiponectin receptors, with special focus on the role of the third receptor, T-cadherin, in vascular disease", Med Mol Morphol, 40, pp.115~120 (2007)
- Ouchi N, "Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway", Circulation, 102, pp.1296~1301 (2000)
- Kudrjashova E, "Expression of adhesion molecule T-cadherin is increased during neointima formation in experimental restenosis", Histochem Cell Biol, 118, pp.281~290 (2002)
- Lee YH, "Visceral adiposity and the severity of coronary artery disease in middle-aged subjects with normal waist circumference and its relation with lipocalin-2 and MCP-1", Atherosclerosis, 213, pp.592~597 (2010)
- 최순자, "The Prevalence, Awareness and Treatment of High Low Density Lipoprotein-Cholesterol in Korean Adults Without Coronary Heart Diseases", Korean Circulation Journal, 42(2), pp.86~94 (2012), 대한심장학회
- Jee SH, "Adiponectin concentrations: a genome-wide association study", Am J Hum Genet, 87, pp.545~552 (2010)
- Wu Y, "Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ", Hum Mol Genet, 19, pp.4955~4964 (2010)
- Morisaki H, "CDH13 gene coding T-cadherin influences variations in plasma adiponectin levels in the Japanese population", Hum Mutat, 33, pp.402~410 (2012)
- Org E, "Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations", Hum Mol Genet, 18, pp.2288~2296 (2009)
- Chung CM, "A genome-wide association study reveals a quantitative trait locus of adiponectin on CDH13 that predicts cardiometabolic outcomes", Diabetes, 60, pp.2417~2423 (2011)
- Adeyemo A, "A genome-wide association study of hypertension and blood pressure in African Americans", PLoS Genet, 5, pp.e1000564~ (2009)
- Breitfeld J, "Genetics of adiponectin", Biochimie, 94, pp.2157~2163 (2012)
- Cardoso CR, "Factors associated with carotid intima-media thickness and carotid plaques in type 2 diabetic patients", J Hypertens, 30, pp.940~947 (2012)
- Su TC, "Age- and gender-associated determinants of carotid intima-media thickness: a community-based study", J Atheroscler Thromb, 19, pp.872~880 (2012)
- Kipmen-Korgun D, "T-cadherin mediates low-density lipoprotein-initiated cell proliferation via the Ca(2+)-tyrosine kinase-Erk1", 2 pathway, 2005, pp.45, 418~430
- de las Fuentes L, "Pathway-based genome-wide association analysis of coronary heart disease identifies biologically important gene sets", Eur J Hum Genet, 20, pp.1168~1173 (2012)
- Díez JJ, "The role of the novel adipocyte-derived hormone adiponectin in human disease", Eur J Endocrinol, 148, pp.293~300 (2003)
- Fava C, "A variant upstream of the CDH13 adiponectin receptor gene and metabolic syndrome in Swedes", Am J Cardiol, 108, pp.1432~1437 (2011)
- Philippova M, "T-cadherin attenuates insulin-dependent signalling, eNOS activation, and angiogenesis in vascular endothelial cells", Cardiovasc Res, 93, pp.498~507 (2012)
- Dong C, "Genetic loci for blood lipid levels identified by linkage and association analyses in Caribbean Hispanics", J Lipid Res, 52, pp.1411~1419 (2011)
