title: SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes.
abstract: OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is known to mediate the development of diabetic nephropathy, we examined the association between the SUMO4 M55V variant and the severity of diabetic nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6, 40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1% in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric group. We detected a significant linear trend for SUMO4 genotype between the macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to-creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol) groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant to be independently associated with the severity of diabetic nephropathy. CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated with severity of diabetic nephropathy in patients with type 2 diabetes.
authors.affiliation: Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd., Kaohsiung 80708, Taiwan.
authors.forename: Hsing-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Chiao-Ling
authors.initials: CL
authors.lastname: Wang
authors.forename: Pi-Jung
authors.initials: PJ
authors.lastname: Hsiao
authors.forename: Yung-Chuan
authors.initials: YC
authors.lastname: Lu
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Chen
authors.forename: Kun-Der
authors.initials: KD
authors.lastname: Lin
authors.forename: Shih-Chie
authors.initials: SC
authors.lastname: Hsin
authors.forename: Ming-Chia
authors.initials: MC
authors.lastname: Hsieh
authors.forename: Shyi-Jang
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D019943:Amino Acid Substitution; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008715:Methionine; D020641:Polymorphism, Single Nucleotide; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*; D014633:Valine
chemical_list: D003062:Codon; D017931:DNA Primers; C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D008715:Methionine; D014633:Valine