The polymorphism rs2268574 in Glucokinase gene is associated with gestational Diabetes mellitus
| Autor: | Henrique Ravanhol Frigeri, Emanuel Maltempi de Souza, Izabella Castilhos Ribeiro dos Santos-Weiss, Nathalia Cavalheiro Auwerter, Geraldo Picheth, Fábio O. Pedrosa, Laysa Toschi Martins, Fabiane Gomes de Moraes Rego |
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| Rok vydání: | 2013 |
| Předmět: |
Genetics
Adult education.field_of_study Linkage disequilibrium dbSNP Haploview Glucokinase Clinical Biochemistry Population Single-nucleotide polymorphism General Medicine Biology Polymorphism Single Nucleotide Minor allele frequency Diabetes Gestational Gene Frequency Pregnancy Genotype Humans Female Genetic Predisposition to Disease education Genetic Association Studies |
| Zdroj: | Clinical biochemistry. 47(6) |
| ISSN: | 1873-2933 |
| Popis: | Dear Editor:Glucokinase (GCK, EC 2.7.1.2) catalyzes the conversion of glucose toglucose-6-phosphate, the first step in glucose metabolism. GCK is con-sidered a glucose sensor in the pancreatic β-cells [1]. The Glucokinasegene (GCK gene; HGNC:4195) is located in chromosome 7 (7p15.3-p15.1). More than 600 mutations in the GCK gene have been reportedand about 2–5% of all Caucasian gestational Diabetes mellitus (GDM)cases are due to Single Nucleotide Polymorphisms (SNPs) in this gene[2]. In previous study, we showed that GDM patients with good glyce-mic control are associated with a low prevalence of GCK mutations de-tected with PCR-SSCP [3]. We focus now on patients that requiresinsulinuse(poorglycemiccontrol)afterGDMdiagnosticsandanalyzedby DNA sequencing, the exons and introns 5 and 6 of the GCK gene forpolymorphisms, in a case–control study. This selected region encodesaminoacids(Exon5:T168,K169;Exon6:N204,D205)forglucosebind-ing in the Glucokinase active site. Healthy Euro-Brazilian pregnantwomen (Control, n = 115) and patients with gestational Diabetesmellitus (GDM, n = 112) were classified according to the American Di-abetesAssociationcriteria[4].Patientswithovertdiabeteswereexclud-ed. The Ethics Committee on Human Research of our institutionapproved this study. PCR (PF: 5′-TCTGAGCCTGTTTCCTCAGC-3′ and PR:5 ′-GGCCCTTGAAGCCTGTTGTA-3 ; 505 bp amplicon) for exons 5 and 6,and flanking regions were performed as described elsewhere [5]. Allsamplesweresequenced(BigDye,3500XL,AppliedBiosystems).Allse-quences showed base-calling quality of more than Q30. The SNPs wereidentified and aligned using CodonCode Alligner v.4.1.1 (CodonCodeCorporation), BlastSNP and Reference SNP database (http://www.ncbi.nlm.nih.gov/).TheSNPgenotypewasnotassociatedwithanthropomet-ric and laboratory parameters (regression analysis, data not shown)in either group. No difference was observed in genotype distribution(P = 0.054). However, a significant difference (P = 0.034) and OddsRatio (CI 95%) 1.5 (1.03–2.17) regarding minor allele (T)wasobservedin the studied population (Table 1). The T-allele frequency observed inhealthy pregnant women (48%) was similar to that for Caucasians(~46%) and higher than for Orientals (~35%) and Sub-Saharan African(~27%) according to HapMap (http://www.hapmap.org/). Although nolinkage disequilibrium for the rs2268574 polymorphism, compared toothers, SNPs in the GCK gene was identified (HaploView v4.2, Day Lab,Cambridge, USA), we observed the rs2268574T N C is located in a puta-tive splicing region (Human Splicing Finder v.2.4.1; http://www.umd.be/HSF/). We hypothesize that the SNP could affect gene transcriptionor more plausibly, it could be in linkage disequilibrium with some |
| Databáze: | OpenAIRE |
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