Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Obesity (Silver Spring). 2013 Sep;21(9):E456-62. doi: 10.1002/oby.20184. Epub 2013 May 13.
Understanding the interplay between adiposity, inflammation, and cardiovascular complications in type 2 diabetes mellitus (T2DM) remains a challenge. Signaling from adipocytes is considered important in this context. Adiponectin is the most abundant adipocytokine and has been associated with various measures of cardiovascular disease (CVD). This study examines the relationships between genetic variants in the adiponectin (ADIPOQ) and adiponectin-related signaling pathway genes and measures of subclinical CVD (vascular calcified plaque and carotid intima-media thickness), plasma lipids, and inflammation in T2DM.
Single-nucleotide polymorphisms (SNPs) in ADIPOQ (n = 45), SNPs tagging ADIPOR1 (n = 6), APIPOR2 (n = 8), APPL1 (n = 6) and known rare coding variants in KNG1 (n = 3) and LYZL1 (n = 3) were genotyped in 1220 European Americans from the family-based Diabetes Heart Study. Associations between SNPs and phenotypes of interest were assessed using a variance components analysis with adjustment for age, sex, T2DM-affected status, and body mass index.
There was minimal evidence of association between SNPs in the adiponectin signaling pathway genes and measures of calcified plaque; eight of the 71 SNPs showed evidence of association with subclinical CVD (P = 0.007-0.046) but not with other phenotypes examined. Nine additional SNPs were associated with at least one of the plasma lipid measures (P = 0.008-0.05).
Findings from this study do not support a significant role for variants in the adiponectin signaling pathway genes in contributing to risk for vascular calcification in T2DM. However, further understanding the interplay between adiposity, plasma lipids, and inflammation may prove important in the prediction and management of cardiovascular complications in T2DM.
了解 2 型糖尿病（T2DM）中肥胖、炎症和心血管并发症之间的相互作用仍然具有挑战性。脂肪细胞的信号传递在这种情况下被认为是很重要的。脂联素是最丰富的脂肪细胞因子，与各种心血管疾病（CVD）的测量指标有关。本研究探讨了脂联素（ADIPOQ）和脂联素相关信号通路基因的遗传变异与 T2DM 患者亚临床 CVD（血管钙化斑块和颈动脉内膜中层厚度）、血浆脂质和炎症之间的关系。
在来自基于家庭的糖尿病心脏研究的 1220 名欧洲裔美国人中，对 ADIPOQ（n = 45）的单核苷酸多态性（SNP）、ADIPOR1（n = 6）、APIPOR2（n = 8）、APPL1（n = 6）的 SNP 进行基因分型，以及 KNG1（n = 3）和 LYZL1（n = 3）中的已知罕见编码变异。使用方差成分分析评估 SNP 与感兴趣表型之间的关联，调整年龄、性别、T2DM 患病状态和体重指数。
在脂联素信号通路基因中的 SNP 与钙化斑块的测量之间几乎没有关联的证据；71 个 SNP 中有 8 个显示与亚临床 CVD 相关（P = 0.007-0.046），但与其他检查的表型无关。另外 9 个 SNP 与至少一个血浆脂质测量值相关（P = 0.008-0.05）。
本研究的结果不支持脂联素信号通路基因中的变异在 T2DM 患者血管钙化风险中的显著作用。然而，进一步了解肥胖、血浆脂质和炎症之间的相互作用可能对 T2DM 心血管并发症的预测和管理很重要。
