Effects of single nucleotide polymorphisms in K(ATP) channel genes on type 2 diabetes in a Turkish population.
OBJECTIVE
ATP-sensitive potassium (K(ATP)) channels of pancreatic β-cells play a key role in glucose-stimulated insulin secretion mechanism. The Kir6.2 protein, forming the K(ATP) channel pore inwardly, and the SUR1 protein that surrounds it forming the outside part of the channel were encoded by ABCC8 and KCNJ11 genes, respectively. Recent studies reported that the single nucleotide polymorphisms (SNPs) established in these genes are associated with defects in insulin secretion and type 2 diabetes mellitus (T2DM). We aimed to investigate the allele profiles and the risk alleles of the ABCC8 and KCNJ11 genes and to highlight the associations with the disease in patients in Konya region of Turkey where T2DM is common.


METHODS
In this study, 169 patients with T2DM and 119 healthy controls were included. A total of 29 SNPs in ABCC8 and KCNJ11 genes were screened by PCR-SSCP technique and sequenced. Biochemical parameters and genotype-phenotype relationships were analyzed using variance analysis.


RESULTS
R1273R silent substitution in exon 31 and 16/-3t→c substitution in noncoding region of exon 16 of ABCC8 gene showed a significant association (OR 4.8 [95% CI 2.41-9.77], p <0.001 and OR 3.5 [95% CI 1.64-7.40], p <0.001 under dominant and recessive models, respectively). We detected a significant association between E/K heterozygote genotype and reduced plasma insulin level in patients with T2DM (p <0.05).


CONCLUSIONS
ABCC8 exons 16 and 31 variants increase susceptibility to T2DM and KCNJ11 E23K decreases insulin secretion in a Turkish population.
Department of Endocrinology, Meram Medical Faculty, Selcuk University, Konya, Turkey. saitgonen@selcuk.edu.tr
Mustafa Sait
MS
Gonen
Hilal
H
Arikoglu
Dudu
D
Erkoc Kaya
Hulya
H
Ozdemir
Suleyman Hilmi
SH
Ipekci
Ahmet
A
Arslan
Seyit Ali
SA
Kayis
Bulent
B
Gogebakan
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D014421:Turkey / Q000453:epidemiology; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human