title: Polymorphisms of myo-inositol oxygenase gene are associated with Type 1 diabetes mellitus.
abstract: Myo-inositol oxygenase (MIOX) is the first and rate-limiting enzyme in myo-inositol (MI) metabolism pathway. The increase in MIOX enzyme activity is in proportion to serum glucose concentrations and may be responsible for the MI depletion found in the diabetic complications. The aim was to investigate whether single nucleotide polymorphisms (SNPs) in the MIOX gene are associated with Type 1 diabetes mellitus (T1D) and its complications. Four hundred thirty Caucasian patients with T1D were recruited: 172 patients had diabetic nephropathy, 140 had diabetic retinopathy/neuropathy, 118 patients had diabetes for ≥20 years without microvascular complications and 224 were normal controls. Three SNPs, rs761745 (C/T), and rs2232873 (A/G) in the promoter and rs1055271 (C/G) in the 3'-untranslated were genotyped commercially. The frequencies of the CC genotype (0.36 vs. 0.44; P=.034) and C allele (0.60 vs. 0.68; P=.011) of rs761745 were significantly lower in patients with T1D compared with normal controls. Patients with T1D had a decreased frequency of the combination genotypes of CC (rs761745), GG (rs2232873) and GC (rs1055271) compared with the normal controls (0.13 vs. 0.22, P=.0027, Pc=0.014). The haplotypes with C/G/G and C/G/C were less common in patients with T1D compared to normal controls (0.59 vs. 0.70, P=.021) and the haplotypes with T/G/C and T/G/G ware more common in patients with T1D compared to normal controls (0.37 vs. 0.26; P=.021). In summary, our results demonstrated that the polymorphism (rs761745) in the promoter region of MIOX gene may be associated with the development of T1D in our studied population.
authors.affiliation: Molecular Medicine Research Group, Institute of Biomedical and Clinical Science, Peninsula Medical School, Tamar Science Park, PL6 8BU Plymouth, UK. byang@pms.ac.uk
authors.forename: Bingmei
authors.initials: B
authors.lastname: Yang
authors.forename: Andrea
authors.initials: A
authors.lastname: Hodgkinson
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Millward
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Demaine
mesh_terms: D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics; D003929:Diabetic Neuropathies / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D050562:Inositol Oxygenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D050562:Inositol Oxygenase