载脂蛋白受体 2 基因变异与葡萄糖耐量受损个体心血管疾病和 2 型糖尿病风险的关系：芬兰糖尿病预防研究。
Association of ADIPOR2 gene variants with cardiovascular disease and type 2 diabetes risk in individuals with impaired glucose tolerance: the Finnish Diabetes Prevention Study.
机构信息
Department of Clinical Nutrition and Food and Health Research Centre, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
出版信息
Cardiovasc Diabetol. 2011 Sep 24;10:83. doi: 10.1186/1475-2840-10-83.
BACKGROUND
Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic effects. Two receptors for adiponectin, ADIPOR1 and ADIPOR2, have been characterized that mediate effects of adiponectin in various tissues. We examined whether genetic variation in ADIPOR2 predicts the development of cardiovascular disease (CVD) and/or Type 2 Diabetes (T2DM) in individuals with impaired glucose tolerance (IGT) participating the Finnish Diabetes Prevention Study (DPS).
METHODS
CVD morbidity and mortality data were collected during a median follow-up of 10.2 years (range 1-13 years) and conversion from IGT to T2DM was assessed during a median follow-up of 7 years (range 1-11 years). Altogether eight SNPs in the ADIPOR2 locus were genotyped in 484 participants of the DPS. Moreover, the same SNPs were genotyped and the mRNA expression levels of ADIPOR2 were determined in peripheral blood mononuclear cells and subcutaneous adipose tissue samples derived from 56 individuals participating in the Genobin study.
RESULTS
In the DPS population, four SNPs (rs10848554, rs11061937, rs1058322, rs16928751) were associated with CVD risk, and two remained significant (p = 0.014 for rs11061937 and p = 0.020 for rs1058322) when all four were included in the same multi-SNP model. Furthermore, the individuals homozygous for the rare minor alleles of rs11061946 and rs11061973 had increased risk of converting from IGT to T2DM. Allele-specific differences in the mRNA expression levels for the rs1058322 variant were seen in peripheral blood mononuclear cells derived from participants of the Genobin study.
CONCLUSIONS
Our results suggest that SNPs in the ADIPOR2 may modify the risk of CVD in individuals with IGT, possibly through alterations in the mRNA expression levels. In addition an independent genetic signal in ADIPOR2 locus may have an impact on the risk of developing T2DM in individuals with IGT.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov NCT00518167.
背景
脂联素是一种具有胰岛素增敏和抗动脉粥样硬化作用的脂肪因子。已经鉴定出脂联素的两种受体 ADIPOR1 和 ADIPOR2，它们介导脂联素在各种组织中的作用。我们研究了葡萄糖耐量受损（IGT）个体中 ADIPOR2 基因变异是否预测心血管疾病（CVD）和/或 2 型糖尿病（T2DM）的发生，这些个体参与了芬兰糖尿病预防研究（DPS）。
方法
在中位随访 10.2 年（范围 1-13 年）期间收集 CVD 发病率和死亡率数据，并在中位随访 7 年（范围 1-11 年）期间评估从 IGT 到 T2DM 的转化。在 DPS 中的 484 名参与者中总共对 ADIPOR2 基因座中的 8 个 SNP 进行了基因分型。此外，在参与 Genobin 研究的 56 名个体的外周血单核细胞和皮下脂肪组织样本中，对相同的 SNP 进行了基因分型，并确定了 ADIPOR2 的 mRNA 表达水平。
结果
在 DPS 人群中，有四个 SNP（rs10848554、rs11061937、rs1058322、rs16928751）与 CVD 风险相关，当所有四个 SNP 都包含在同一个多 SNP 模型中时，其中两个仍然具有统计学意义（rs11061937 的 p = 0.014，rs1058322 的 p = 0.020）。此外，rs11061946 和 rs11061973 罕见的次要等位基因纯合子个体发生从 IGT 到 T2DM 的转化率增加。在 Genobin 研究中，来自参与者的外周血单核细胞中观察到 rs1058322 变体的等位基因特异性 mRNA 表达水平差异。
结论
我们的研究结果表明，ADIPOR2 中的 SNP 可能通过改变 mRNA 表达水平来改变 IGT 个体的 CVD 风险。此外，ADIPOR2 基因座中的独立遗传信号可能对 IGT 个体发生 T2DM 的风险产生影响。
试验注册号
ClinicalTrials.gov NCT00518167。
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