The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus
The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus
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GHRL基因Leu72Met多态性可预防中国2型糖尿病患者发生糖尿病肾病
DOI：
10.1007/s11010-013-1865-6
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发表时间：
2014-02
期刊：
影响因子：
3.9
通讯作者：
Limei Liu
中科院分区：
文献类型：
--
作者：
Langen Zhuang;Limei Liu
前促生长素释放肽（GHRL）Leu 72 Met多态性（rs 696217）与肥胖、健康或糖尿病受试者中葡萄糖诱导的胰岛素分泌减少以及2型糖尿病中血清肌酐（Scr）水平降低相关。我们评估了Leu 72 Met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的相关性，以及这种变异是否有助于2型糖尿病患者糖尿病肾病（DN）的发展。对291例非糖尿病对照者和466例2型糖尿病患者进行了病例对照研究，其中238例DN伴明显蛋白尿（DN组;蛋白尿排泄率[AER] ≥ 300 mg/24 h），228例未患DN，但糖尿病超过10年（非DN组）。使用TaqMan PCR测定进行基因分型。Leu/Leu、Leu/Met和Met/Met基因型频率在非DN组和DN组之间存在显著差异（p = 0.011）。DN组中变异基因型（Leu/Met，Met/Met）的频率显著低于非DN组（23.5% vs. 36.0%，p = 0.003）。Met/Met非糖尿病对照受试者的BMI和Scr水平低于Leu/Leu或Leu/Met个体（p < 0.05），eGFR水平高于Leu/Leu或Leu/Met个体（p < 0.05）。Leu/Met和Met/Met 2型糖尿病患者的AER和Scr水平显著低于Leu/Leu 2型糖尿病患者，eGFR水平显著高于Leu/Leu 2型糖尿病患者（均p < 0.001）。GHRL Leu 72 Met基因多态性可能有助于维持正常的肾功能，并可能通过减少蛋白尿和改善肾功能来预防中国2型糖尿病患者发生DN。
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.
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