Jang Yangsoo, Chae Jey Sook, Koh Soo Jeong, Hyun Yae Jung, Kim Ji Young, Jeong Yeo Jin, Park Sungha, Ahn Chul-Min, Lee Jong Ho
Cardiovascular Genome Center, Cardiovascular Hospital, Severance Hospital, Seoul, Korea.
Clin Chim Acta. 2008 May;391(1-2):85-90. doi: 10.1016/j.cca.2008.02.011. Epub 2008 Feb 16.
Concentrations of adiponectin, the protein product of the adipocyte C1q and collagen-domain-containing (ADIPOQ) gene are associated with type 2 diabetes and coronary artery disease. We investigate the association of single-nucleotide polymorphisms (SNPs) in the ADIPOQ gene with adiponectin concentrations, and to parameters of metabolic syndrome.
867 unrelated, non-diabetic Korean women, 20 to 69 y, were genotyped for 8 SNPs in the ADIPOQ gene (-11391G>A, -11377C>G, H241P, Y111H, G90S, R221S, 45T>G, 276G>T). Adiponectin, a homeostasis model assessment of insulin resistance (HOMA-IR), and metabolic parameters were measured.
Carriers of genotype T/T at position 276 had significantly higher adiponectin concentrations than G/G carriers (P=0.005). Homozygous carriers of the TG haplotype (i.e., individuals who were T/T at 45 and G/G at 276) and heterozygous carriers of the TG haplotype (TG/X) had lower adiponectin concentrations than non-TG carriers (P<0.001). Significant associations between SNP at 276 and serum concentrations of triglyceride (P=0.013), insulin (P=0.013) and HOMA-IR (P=0.012) were found. The 45-276 haplotypes had associations identical to the 276G>T SNP. In subgroup analysis, subjects carrying the TG haplotype had significantly lower adiponectin concentrations than non-TG carriers in both normal weight (P<0.001) and overweight-obese (P=0.009) subgroups. The association of the TG haplotype with increasing insulin concentrations was significant among overweight-obese subjects (P=0.004), but was not significant among normal weight subjects. A similar association was found between the 45-276 haplotype and HOMA-IR.
There is a strong association of the adiponectin SNP276 genotypes and the adiponectin 45-276 haplotypes with circulating adiponectin concentrations in non-diabetic Korean women. In addition, this haplotype is associated with increased insulin concentrations and insulin resistance index only in overweight-obese individuals.
脂联素是脂肪细胞C1q和含胶原结构域(ADIPOQ)基因的蛋白质产物,其浓度与2型糖尿病和冠状动脉疾病相关。我们研究了ADIPOQ基因中的单核苷酸多态性(SNP)与脂联素浓度以及代谢综合征参数之间的关联。
对867名年龄在20至69岁之间、无亲缘关系的非糖尿病韩国女性进行ADIPOQ基因中8个SNP(-11391G>A、-11377C>G、H241P、Y111H、G90S、R221S、45T>G、276G>T)的基因分型。测量脂联素、胰岛素抵抗的稳态模型评估(HOMA-IR)以及代谢参数。
276位点基因型为T/T的携带者的脂联素浓度显著高于G/G携带者(P=0.005)。TG单倍型的纯合携带者(即45位点为T/T且276位点为G/G的个体)和TG单倍型的杂合携带者(TG/X)的脂联素浓度低于非TG携带者(P<0.001)。发现276位点的SNP与甘油三酯血清浓度(P=0.013)、胰岛素(P=0.013)和HOMA-IR(P=0.012)之间存在显著关联。45-276单倍型的关联与276G>T SNP相同。在亚组分析中,携带TG单倍型的受试者在正常体重(P<0.001)和超重-肥胖(P=0.009)亚组中的脂联素浓度均显著低于非TG携带者。TG单倍型与胰岛素浓度升高之间的关联在超重-肥胖受试者中显著(P=0.004),但在正常体重受试者中不显著。在45-276单倍型与HOMA-IR之间也发现了类似的关联。
在非糖尿病韩国女性中,脂联素SNP276基因型和脂联素45-276单倍型与循环脂联素浓度之间存在强烈关联。此外,这种单倍型仅在超重-肥胖个体中与胰岛素浓度升高和胰岛素抵抗指数相关。