Objective: Glucose metabolism increases ATP/ADP ratio within the β-cells and causes
ATP-sensitive K+ (KATP) channel closure and consequently insulin secretion. The enhanced activity
of the channel may be a mechanism contributing to the reduced first-phase of insulin secretion observed
in T2DM. There is no study to date in the Kurdish ethnic group regarding the relationship between
SNP Ala1369Ser (rs757110 T/G) of SUR1 gene and T2DM, and additionally, the results of this
association in other populations are inconsistent. Therefore, our aim in this study was to explore the
possible association between SNP Ala1369Ser and type 2 diabetes in an Iranian Kurdish ethnic group.
Methods: In this study, we checked out the frequency of alleles and genotypes of SNP Ala1369Ser in
T2DM individuals (207 patients; men/women: 106/101) and non-T2DM subjects (201 controls;
men/women: 97/104), and their effects on anthropometric, clinical, and biochemical parameters. Genomic
DNA was extracted from the leukocytes of blood specimens using a standard method. We amplified
the ABCC8 rs757110 polymorphic site (T/G) using a polymerase chain reaction (PCR) method
and a designed primer pair. To perform the PCR-RFLP method, the amplicons were subjected to restriction
enzymes and the resulting fragments separated by gel electrophoresis.
Results: The frequency of the G-allele of Ala1369Ser polymorphism was significantly (0.01) higher in
the case group than the control group (19% vs. 9%, respectively). In the dominant model (TT vs.
TG+GG), there was a significant relationship between this SNP and an increased risk of T2DM (P =
0.00). T2DM patients with TG+GG genotypes had significantly higher fasting plasma insulin and
HOMA-IR than those who had the TT genotype (P = 0.02 and 0.01, respectively).
Conclusion: Our study is the first study to investigate the association between Ala1369Ser ABCC8
genetic variation and T2DM in the Kurdish population of western Iran. The obtained results clearly
show that Ala1369Ser polymorphism of ABCC8 is associated with an increased risk of T2DM in this