title: The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Endocrinology & Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Langen
authors.initials: L
authors.lastname: Zhuang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Changhua
authors.initials: C
authors.lastname: Yu
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Taishan
authors.initials: T
authors.lastname: Zheng
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Weijing
authors.initials: W
authors.lastname: Zhao
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.forename: Kunsan
authors.initials: K
authors.lastname: Xiang
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
authors.forename: Limei
authors.initials: L
authors.lastname: Liu
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D060467:Disease Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D054439:Ghrelin / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors / Q000235:genetics*
chemical_list: D054439:Ghrelin; D011498:Protein Precursors