title: Synaptosomal Protein of 25 kDa (Snap25) Polymorphisms Associated with Glycemic Parameters in Type 2 Diabetes Patients.
abstract: A possible role of Snap25 polymorphisms in type 2 diabetes mellitus (T2DM) was evaluated by analyzing three SNPs within intron 1 in a region known to affect the gene expression in vitro. Genomic DNA from 1019 Saudi individuals (489 confirmed T2DM and 530 controls) was genotyped for SNPs rs363039, rs363043, and rs363050 in Snap25 using the TaqMan Genotyping Assay. Significantly higher levels of fasting glucose and HbA1c were detected in T2DM patients carrying the rs363050 (AG/GG) genotypes compared to the (AA) genotype (f = 4.41, df = 1, and p = 0.03 and f = 5.31, df = 1, and p = 0.03, resp.). In these same patients, insulin levels were significantly decreased compared to the (AA) individuals (f = 7.29, df = 1, and p = 0.009). Significant associations were detected between rs363050 (AG/GG) genotypes and increasing fasting glucose levels (p = 0.01 and OR: 1.05), HbA1c levels (OR: 5.06 and p = 0.02), and lower insulinemia (p = 0.03 and OR: 0.95) in T2DM patients. The minor Snap25 rs363050 (G) allele, which results in a reduced expression of Snap25, is associated with altered glycemic parameters in T2DM possibly because of reduced functionality in the exocytotic machinery leading to suboptimal release of insulin.
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Nasser M
authors.identifier: 0000-0001-5472-1725
authors.initials: NM
authors.lastname: Al-Daghri
authors.affiliation: Fondazione Don C Gnocchi, IRCCS, 20148 Milano, Italy.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Costa
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Majed S
authors.initials: MS
authors.lastname: Alokail
authors.affiliation: Fondazione Don C Gnocchi, IRCCS, 20148 Milano, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Zanzottera
authors.affiliation: School of Biological Sciences, University of Southampton, Southampton SO17 1 BJ, UK.
authors.forename: Amal M
authors.initials: AM
authors.lastname: Alenad
authors.affiliation: Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Abdul Khader
authors.initials: AK
authors.lastname: Mohammed
authors.affiliation: Fondazione Don C Gnocchi, IRCCS, 20148 Milano, Italy; Università degli Studi di Milano, 20122 Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Fondazione Don C Gnocchi, IRCCS, 20148 Milano, Italy.
authors.forename: Franca R
authors.initials: FR
authors.lastname: Guerini
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000032:analysis*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood*; D007438:Introns; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D050825:Synaptosomal-Associated Protein 25; C494208:SNAP25 protein, human; C517652:hemoglobin A1c protein, human