الفهرس 
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Abstract
Type 2 diabetes form an epidemic metabolic disease threatens to increase the burden on healthcare systems dramatically worldwide. Therefore, the prevention of type 2 diabetes has become a major challenge for clinicians and public health policy makers all over the world by early diagnosis before the development of the disease. Consequently, many candidate gene, linkage and recently genome wide association studies have been conducted to reveal many genes that interact with environmental factors to manifest the disease in different ethnic populations.
The present work was aimed to study the association between the common KCNJ11 (E23K) and ABCC8 (S1369A) genetic polymorphisms in the development of type 2 diabetes in a small of Egyptian population.
The present study included fifty three unrelated Egyptians (41 women and 12 men) over age 40 years with type 2 diabetes selected from those attending the outpatient clinic in the National Institute of Diabetes & Endocrinology. Thirty non diabetic Egyptian (11 women and 19 men) with age matching with the case group and negative family history of T2D among their first degree relatives selected from individuals work in Misr University for Science & Technology.
All patients and controls were subjected to the following:
1. Detailed questionnaire for each patient: the age, sex, body weight, height, age of onset of the disease, duration of disease, complications and family history for type 2 diabetes.
2. Biochemical analysis of the fasting plasma glucose, lipid profile (LDL, HDL, T.G. and total cholesterol) and fasting insulin level for both case and control groups.
3. Estimating the HOMA-IR for both case and control groups.
4. Molecular analysis for E23K variant in the KCNJ11 gene by using Taqman Allelic Discrimination assay Real-time PCR.
5. Molecular analysis for S1369A variant in the ABCC8 gene by using Taqman Allelic Discrimination assay Real-time PCR.
6. Statistical analysis of the data.
The results of the present study were:
• The age of the studied patients ranged from 41 to 74 (mean= 54.21 ± 7.59 years).the age of the control group ranged from 40 to 66 (mean=50.83 ± 7.5 years)
• There were more female 77.4% than male 22.6% in patient group in contrast with control group 36.7 % female versus 63.3% male. Most of the patients were obese with (mean BMI= 36.53 ± 6.32Kg/m2) compared with control group( mean BMI=28.17 ± 3.58 Kg/m2).
• The medical history of our patients results recorded as 60.4% had hypertension, 11.6% had cardiovascular disease, 15.1% had retinopathy, and7.5% had diabetic foot with mean duration of the disease (14.31 ± 9.26) and the age of onset (50.57 ± 10.7 years).
• The biochemical analysis results showed significant differences between case and controls group (P<0.05) for fasting plasma glucose (FPG), fasting insulin level, the HOMA-IR value as well as for the lipid profile including [low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and total cholesterol (T-CHO) level], while no significant differences between two group regarding with high density lipoprotein cholesterol (HDL-C) was found (P=0.054).
• The genotype distribution of KCNJ11 (E23K) polymorphism was as follow: 67.9% had )CC(, 26.4% had )CT( and 5.7% had )TT( genotype in patient group which were not significantly different with control group where, 76.7% had CC genotype , 20.0% had )CT( genotype and 3.3% had )TT( genotype (P=0.688) . As well as [C]allele frequency was found in 81.1% and [T] allele was in 18.9 % of patients which was not significantly different in the control group where the [C] allele frequency was found in 86.7% and [T] allele was in 13.3% with overall odd ratio OR=1.000 with [95%CI 0.621 – 3.678]).
• Also there were no significant differences in genotype distribution regarding ABCC8 (S1369A) polymorphism where )AA( genotype was found in 54.7%, )AC( genotype in 41.5% and )CC( genotype in 3.8 of patients compared with the control group where AA genotype was found in 73.3%, )AC( genotype in 23.3% and )CC( genotype in 3.3% subjects (P=0.234). As well as [A] allele frequency was found in 75.5% and [C] allele was in 24.5% of patients. Likewise, the [A] allele frequency was found in 85.0% and [C] allele was in 15.0% of non-diabetic subjects with overall odd ratio (OR=1.000 with [95%CI 0.799 – 4.246]).
• The genotype-phenotype correlation analysis results showed no significant association of KCNJ11 (E23K) polymorphism with any T2DM related phenotypes expect the BMI was higher in EE genotype (P=0.005) rather than other genotypes in control group only. In Addition, the fasting insulin level was lower in EK genotype rather than homozygous EE genotypes in control group (P=0.003).
• Regarding the ABCC8 (S1369A) polymorphism, there were no genotype-phenotype association expect for BMI that was higher in wild type genotype A/A than in those with A/C heterozygous genotype (P=0.020) in control group.
• The interactions between two SNPs of KCNJ11 [E23K] and ABCC8 [S1369A] genes respictevely, on the risk of type 2 diabetes showed no significant results (P<0.05) in the case-control Egyptian samples.
• The linkage disequilibrium result showed relatively strong LD pattern between two S1369A and E23K genetic polymorphisms (D’= 0.221) in patient group. Moreover the genetic correlation coefficient between the possible alleles frequency of both (E23K-S1369A) variants showed that 65% of individuals in our study with two copies of K23 also possess two copies of A1369 in other locus that confirmed the linkage disequilibrium pattern and explain the identical phenotype genotype association results in our study.