Adiponectin Gene Variation −4522C/T Is Associated with Type 2 Diabetic Obesity and Insulin Resistance in Chinese

Hekun Liu^{a, b
,},
Suyun Chen^{b, c
,},
Sizhong Zhang^{a, a
, ,},
Cuiying Xiao^a,
Yan Ren^d,
Haoming Tian^d,
Xuefei Li^b

a.
Department of Medical Genetics, West China Hospital, Sichuan University, and Division of Human Morbid Genomics, State Key Laboratory of Biotherapy of Human Diseases, Chengdu 610041, China
b.
Department of Cell Biology and Genetics, and Center of Neuroscience, Fujian Medical University, Fuzhou 350004, China
c.
Department of Microbiology And Immunology, Xiamen Medical College, Xiamen 361001, China
d.
Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China

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Corresponding author: E-mail address: szzhang@mcwcums.com (Sizhong Zhang)

摘要

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Abstract: The authors investigated the possible association of −4522C/T variation of adiponectin gene with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). Genotyping of SNP −4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the T/T genotype and T allele with type 2 diabetes combined with obesity (BMI ≥ 25 kg/m²) was found (P = 0.014 and P = 0.034, respectively). Also the homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele (P = 0.0069). The authors' findings for the first time demonstrated that SNP −4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But −4522C/T polymorphism did not contribute to the susceptibility of CHD.
- adiponectin /
- single nucleotide polymorphism /
- coronary heart disease /
- type 2 diabetes /
- insulin resistance

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参考文献(31)

[1]	Kissebah, AH, Sonnenberg, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome Proc Natl Acad Sci USA, 97 (2000),pp. 14478-14483
[2]	Berg, AH, Combs, et al. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action Nat Med, 7 (2001),pp. 947-953
[3]	Fruebis, J, Tsao, et al. Proteolytic cleavage product of 30 kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice Proc Natl Acad Sci USA, 98 (2001),pp. 2005-2010
[4]	Yamauchi, T, Kamon, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis J Biol Chem, 278 (2003),pp. 2461-2468
[5]	Kissebah, AH, Sonnenberg, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome Proc Natl Acad Sci USA, 97 (2000),pp. 14478-14483
[6]	Francke, S, Manraj, et al. A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27 Hum Mol Genet, 10 (2001),pp. 2751-2765
[7]	Bahia, L, Aguiar, et al. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome Clinics, 61 (2006),pp. 433-440
[8]	Ouchi, N, Kihara, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin Circulation, 100 (1999),pp. 2473-2476
[9]	Ouchi, N, Kihara, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages Circulation, 103 (2001),pp. 1057-1063
[10]	Nakatani, K, Noma, et al. Adiponectin gene variation associates with the increasing risk of type 2 diabetes in non-diabetic Japanese subjects Int J Mol Med, 15 (2005),pp. 173-177
[11]	Zacharova, J, Chiasson, et al. The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial Diabetes, 54 (2005),pp. 893-899
[12]	Filippi, E, Sentinelli, et al. The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age <or=50 years) J Mol Med, 83 (2005),pp. 711-719
[13]	Liu, H, Zhang, et al. Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese Metabolism, 54 (2005),pp. 568-572
[14]	Su, Z, Zhang, et al. A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity J Lipid Res, 43 (2002),pp. 1595-1601
[15]	World health organization. Definition, diagnosis and classification of diabetes mellitus and its complications report of WHO consultation Part 1: diagnosis and classification of diabetes mellitus. Geneva, 1999.
[16]	Matthews, DR, Hosker, et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man Diabetologia, 28 (1985),pp. 412-419
[17]	Hotta, K, Funahashi, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients Arterioscler Thromb Vasc Biol, 20 (2000),pp. 1595-1599
[18]	Kubota, N, Terauchi, et al. Disruption of adiponectin causes insulin resistance and neointimal formation J Biol Chem, 277 (2002),pp. 25863-25866
[19]	Yamauchi, T, Kamon, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects Nature, 423 (2003),pp. 762-769
[20]	Matsuzawa, Y Adiponectins and metabolic syndrome Semin Vasc Med, 5 (2005),pp. 34-39
[21]	Arita, Y, Kihara, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity Biochem Biophys Res Commun, 257 (1999),pp. 79-83
[22]	Iacobellis, G, Pistilli, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease Cytokine, 29 (2005),pp. 251-255
[23]	Yang, X, Jansson, et al. Effect of the interleukin-6 (-174) g/c promoter polymorphism on adiponectin and insulin sensitivity Obes Res, 13 (2005),pp. 813-817
[24]	Gonzalez-Sanchez, JL, Zabena, et al. An SNP in the adiponectin gene is associated with decreased serum adiponectin levels and risk for impaired glucose tolerance Obes Res, 13 (2005),pp. 807-812
[25]	Kondo, H, Shimomura, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome Diabetes, 51 (2002),pp. 2325-2328
[26]	Hara, K, Boutin, et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population Diabetes, 51 (2002),pp. 536-540
[27]	Xia, H, Mo, et al. Correlation between single nucleotide polymorphism of adiponectin gene and type 2 diabetes in Chinese Chin J Endocrinol Metab, 20 (2004),pp. 236-237
[28]	Lee, YY, Lee, et al. Genetic association study of adiponectin polymorphisms with risk of Type 2 diabetes mellitus in Korean population Diabet Med, 22 (2005),pp. 569-575
[29]	Ohashi, K, Ouchi, et al. Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease J Am Coll Cardiol, 43 (2004),pp. 1195-1200
[30]	Lacquemant, C, Froguel, et al. The adiponectin gene SNP+45 is associated with coronary artery disease in Type 2 (non-insulin-dependent) diabetes mellitus Diabet Med, 21 (2004),pp. 776-781
[31]	Filippi, E, Sentinelli, et al. The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age <or=50 years) J Mol Med, 83 (2005),pp. 711-719