Summary and conclusion
Sirtuins (SIRTs) are members of the silent information regulator 2 family. SIRT1 exerts anti-apoptotic, anti-oxidative, and anti-inflammatory effects against cellular injury, and protects the cells through the regulation of mitochondrial biogenesis, autophagy, and metabolism.SIRT1 also promotes vasodilation and protects vascular tissues. In humans with diabetic kidney disease (DKD), its expression tends to be decreased in renal cells.
SIRT1 gene polymorphism was detected using real -timePCR in a total number of 50 subjects, 40 type 2 diabetic patients with diabetic kidney disease (DKD) and 10 diabetics without DKD as a control subjects. The subjects were divided in to 3 groups; (Group I), included (20) type 2 diabetic patients with DKD, with albuminuria [A/C ratio > 30 mg/g], (Group II), included (20) type 2 diabetic patients with DKD, without albuminuria [A/C ratio < 30 mg/g], and (Group III), (10) type 2 diabetic patients as a controls without DKD. The following investigations were done: fasting blood glucose (mg/dl), total cholesterol (mg/dl), triglycerides (mg/dl), HDL-c (mg/dl), LDL-c (mg/dl), serum creatinine (mg/dl), HbA1c (%), ACR (mg/g), eGFR (ml/min/1.73m²).
As regards age, sex, BMI and blood pressure there were no significant difference between the three studied groups, while there was significant increase in duration of DM, HbA1c, 2hr PPG, TC, TG, LDC,Urea,Creatinine and ACR and significant decrease in HDL-C and eGFR in diabetics with DKD when compared to those without DKD.
Comparing (Group I) with (Group II) FBG and ACR were significantly higher in DKD with albuminuria when compared to those
Summary and conclusion
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without albuminuria, while duration of DM, HbA1c, 2hr PPG, Lipid profile urea, creatinine and eGFR did not differ significantly between DKD with and without albuminuria.
The genotype distribution of SIRT1 gene polymorphism was different between the control group (AA 30%, GA 30%, GG40%) and the DKD patients (AA 5%, 40%, GG 55%). The frequency of the mutant G allele in control group was 55%, while it was 75% in DKD group.
There was statistical significant increase in GG and decrease in AA frequency in patients with DKD when compared to patients without DKD P values were 0.047 and 0.047respectively, OR (95% C.I) were3.573 (1.018-12.927) and 0.280 (0.080-.983) respectively. Moreover, there was statistical significant increase in G allele frequency in patients with DKD when compared to patients without DKD (P value =0.086), OR (95% C.I) = 2.455 (0.889-6.779) and 0.594 (0.328-1.076) respectively.
The genotype distribution of SIRT1 gene polymorphism in DKD patients with albuminuria (group I), was (AA 5%, GA 25%, GG 70%) versus (AA 5%, GA 55%, GG 40%) in those without albuminuria (group II). The frequency of the mutant G allele in group I was 82.5%, while it was 67.5% in group II.
There was statistical significant increase in GG and decrease in GA frequency in DKD patients with albuminuria when compared to those without albuminuria P values were 0.047 and 0.049 respectively, OR (95% C.I) were 2.180( 1.976-4.869) and 0.433 (0.188-0.998)respectively.
According to the result of the present study, diabetic patients carrying G allele (GG and GA) had significantly higher urea, creatinine
Summary and conclusion
concentration and significantly lower eGFR when compared to those carrying AA genotype.
As regarding the eGFR, it was significantly lower in DKD groups (with and without albuminuria) when compared to those without DKD but didn’t differ significantly between albumnuric and non albumnuric DKD, while UACR is significantly higher in DKD with albuminuria (group I) compared to DKD without albuminuria (group II).
Logistic regression analysis was conducted for prediction of DKD development within diabetic patients revealed that longer DM duration, higher HbA1C, ACR, lower eGFR, GA+GG genotypes were associated with risk of DKD development within diabetic patients in univariable analysis However, multivariable analysis revealed that only lower eGFR, GA+GG genotypes were considered independent risk factors for prediction of DKD development within diabetic patients.
Logistic regression analysis was conducted for prediction of albuminuria development within diabetic DKD patients revealed that GG genotypes was considered independent risk factors for prediction of albuminuria development within diabetic DKD patients in uni- and multivariable analyses. |
