Research Unit of Diabetes and Endocrine Disease, IRCCS Casa Sollievo della Sofferenza, Viale Padre Pio, 71013 San Giovanni Rotondo, Italy.
Diabetologia. 2011 Apr;54(4):812-8. doi: 10.1007/s00125-010-2037-9. Epub 2011 Jan 13.
AIMS/HYPOTHESIS: Insulin resistance is associated with reduced serum adiponectin and increased albuminuria levels. Thus, one would anticipate an inverse relationship between circulating adiponectin and albuminuria. However, several studies have described a 'paradoxical' elevation of serum adiponectin in patients with elevated albuminuria. These findings may have been confounded by the presence of diseases and related treatments known to affect circulating adiponectin and albuminuria. We therefore studied the relationship between circulating adiponectin and albuminuria in the absence of such confounders.
To this purpose, the relationship between adiponectin isoforms and albumin:creatinine ratio (ACR) was investigated in a family-based sample of 634 non-diabetic untreated white individuals with normal kidney function. We also investigated whether the two variables share a common genetic background and addressed the specific role of the gene encoding adiponectin on that background by genotyping several ADIPOQ single nucleotide polymorphisms (SNPs).
ACR was directly associated with high molecular weight (HMW) adiponectin isoform (p = 0.024). The two variables shared some genetic correlation (ρ(g) = 0.38, p = 0.04). ADIPOQ promoter SNP rs17300539 was associated with HMW adiponectin (p = 4.8 × 10(-5)) and ACR (p =0.0027). The genetic correlation between HMW adiponectin and ACR was no longer significant when SNP rs17300539 was added to the model, thus reinforcing the role of this SNP in determining both traits.
CONCLUSIONS/INTERPRETATION: Our study shows a positive, independent correlation between HWM adiponectin and ACR. ADIPOQ variability is associated with HMW adiponectin and ACR, and explains some of the common genetic background shared by these traits, thus suggesting that ADIPOQ and HMW adiponectin modulate albuminuria levels.
目的/假设：胰岛素抵抗与血清脂联素水平降低和白蛋白尿水平升高有关。因此，人们预计循环脂联素与白蛋白尿之间存在负相关关系。然而，几项研究描述了白蛋白尿升高患者血清脂联素的“反常”升高。这些发现可能受到已知影响循环脂联素和白蛋白尿的疾病和相关治疗的影响。因此，我们在没有这些混杂因素的情况下研究了循环脂联素与白蛋白尿之间的关系。
为此，我们在一个由 634 名非糖尿病未接受治疗的白种个体组成的家族样本中研究了脂联素亚型与白蛋白/肌酐比值（ACR）之间的关系，这些个体的肾功能正常。我们还研究了这两个变量是否具有共同的遗传背景，并通过基因分型几种 ADIPOQ 单核苷酸多态性（SNP）来解决该背景下编码脂联素的基因的特定作用。
ACR 与高分子量（HMW）脂联素亚型直接相关（p=0.024）。这两个变量具有一定的遗传相关性（ρ（g）=0.38，p=0.04）。ADIPOQ 启动子 SNP rs17300539 与 HMW 脂联素（p=4.8×10（-5））和 ACR（p=0.0027）相关。当将 SNP rs17300539 添加到模型中时，HMW 脂联素和 ACR 之间的遗传相关性不再显著，从而增强了该 SNP 对确定这两个特征的作用。
结论/解释：我们的研究显示 HWM 脂联素与 ACR 之间存在正相关、独立的相关性。ADIPOQ 变异与 HMW 脂联素和 ACR 相关，并解释了这些特征之间部分共同的遗传背景，因此提示 ADIPOQ 和 HMW 脂联素调节白蛋白尿水平。
