Department of Endocrinology & Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, 600 Yishan Road, Shanghai, 200233, China.
Mol Cell Biochem. 2014 Feb;387(1-2):19-25. doi: 10.1007/s11010-013-1865-6. Epub 2013 Oct 17.
The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.
前胃泌素原（GHRL）Leu72Met 多态性（rs696217）与肥胖、健康或糖尿病患者葡萄糖诱导的胰岛素分泌减少以及 2 型糖尿病患者血清肌酐（Scr）水平降低有关。我们评估了 Leu72Met 多态性与非糖尿病对照个体和 2 型糖尿病患者胰岛素敏感性指标的相关性，以及这种变异是否有助于 2 型糖尿病患者发生糖尿病肾病（DN）。对 291 名非糖尿病对照个体和 466 名 2 型糖尿病患者进行了病例对照研究，其中 238 名患有显性白蛋白尿的糖尿病肾病（DN 组；白蛋白排泄率 [AER]≥300mg/24h），228 名未患有糖尿病肾病，但患有糖尿病 10 年以上（非 DN 组）。使用 TaqMan PCR 测定法进行基因分型。非 DN 组和 DN 组之间的 Leu/Leu、Leu/Met 和 Met/Met 基因型频率有显著差异（p=0.011）。DN 组变异基因型（Leu/Met、Met/Met）的频率明显低于非 DN 组（23.5%比 36.0%，p=0.003）。Met/Met 非糖尿病对照个体的 BMI 和 Scr 水平较低，eGFR 水平较高，而 Leu/Leu 或 Leu/Met 个体则较低（p<0.05）。Leu/Met 和 Met/Met 型 2 型糖尿病患者的 AER 和 Scr 水平明显低于 Leu/Leu 型 2 型糖尿病患者，eGFR 水平明显高于 Leu/Leu 型 2 型糖尿病患者（均 p<0.001）。GHRL Leu72Met 多态性可能有助于维持正常肾功能，并通过减少白蛋白尿和改善肾功能，从而有助于预防中国 2 型糖尿病患者发生糖尿病肾病。
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