Association of the genetic variants of insulin receptor substrate 1 (IRS-1) with type 2 diabetes mellitus in a Saudi population.
Type 2 diabetes mellitus (T2DM) is a chronic degenerative disease, phenotypically and genetically heterogeneous, characterized by high levels of glucose and metabolic complications. Insulin receptor substrate 1 (IRS-1) plays a key role in the insulin-stimulated signal transduction pathway. A glycine-to-arginine substitution at codon 972 (G972R) (rs1801278) in the IRS-1 gene has been associated with impaired insulin action. Another SNP rs2943641 in the IRS-1 gene has been found to be associated with T2DM and insulin resistance in genome-wide association studies. The aim of the present study was to evaluate whether rs1801278 and rs2943641 are associated with increased risk of T2DM in the Saudi population. The study included 376 T2DM cases and 380 healthy controls. Genomic DNA was isolated using a commercially available kit supplied by Norgen Biotech Corp. Genotyping was performed by PCR and RFLP analysis. There was a significant difference in the genotypic distribution as well as allelic frequency between the T2DM cases and controls in case of both the polymorphisms for rs1801278 (1.752, 95 % CI 1.002-3.121; p = 0.04), and for rs2943641 (OR = 1.482, 95 % CI 1.176-1.867; p = 0.001). In conclusion, both the (rs1801278 and rs2943641) polymorphisms are associated with T2DM in the Saudi population.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433, Kingdom of Saudi Arabia.
Khalid Khalaf
KK
Alharbi
Imran Ali
IA
Khan
Anjana
A
Munshi
Fawiziah Khalaf
FK
Alharbi
Yazeed
Y
Al-Sheikh
May Salem
MS
Alnbaheen
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012529:Saudi Arabia
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins