الفهرس 
I- IntroductionOnly 14 pages are availabe for public view
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Abstract
Diabetic kidney disease is the most common cause of ESRD in the
world, and could account for disability and high mortality rate in patients
with diabetes. Therefore identification of diabetic kidney disease risk
factors is a priority for the patient and the healthcare system.
Oxidative stress plays a main role in the pathogenesis of diabetic
nephropathy. As a consequence, a cellular adaptive response occurs
requiring functional chaperones, so that the induction of HSPs is a
maintained response in counteracting this oxidative stress.
HSP70 proteins are the major stress-inducible proteins that regulate
cellular homeostasis promoting cell survival under stressful stimuli. Also,
they inhibit apoptosis.
Previous studies have documented the crucial role of HSPs in renal
cell survival in several acute and chronic renal diseases.
HSP70-1 and HSP70-2 are highly homologous single exon genes
that are found in a tandem arrangement within a 14 kb region on
chromosome 6p21.3 with an additional homologous heat shock gene
HSP70-hom located in the reverse orientation approximately 4 kb
upstream of HSP70-1 whose expression is constitutive.
These genes are polymorphic, with some variants potentially
accounting for a change in function and susceptibility to stress tolerance.
HSP70 gene polymorphisms were found to be risk factors in several
human disorders and they might play an important role in susceptibility to
and/or progression of diabetic nephropathy.
This study was done to evaluate the association between the two
polymorphisms: HSP70-2 +1267 A/G and HSP70-hom +2437 T/C
polymorphisms and susceptibility of type 2 diabetics to develop DN.
This study was carried out on 80 subjects divided into three groups:
30 diabetic patients with diabetic nephropathy, 30 diabetic patients
without diabetic nephropathy and 20 age and gender matched healthy
controls. Measurements of serum total cholesterol, serum urea and
creatinine, ACR, fasting and 2 hours postprandial blood glucose, glycated
hemoglobin (HbA1c) and genotyping of HSP70-2 +1267 A/G and
HSP70-hom +2437 T/C polymorphisms by PCR/RFLP were done for all
subjects.
The results of this study can be summarized as follows:
*As regards to the fasting blood glucose (FBG), postprandial blood
glucose (PPBG) and HbA1c%:
There was highly significant statistical difference as regards the
levels of FBG, postprandial blood glucose PPBG and HbA1c% on
comparing the three studied groups & significant statistical increase in
FBG, PPBG and HbA1c in diabetics with nephropathy when compared
with diabetics without nephropathy. There was also significant statistical
difference when each diabetic group (with nephropathy or without
nephropathy) is compared with controls.
*As regards to the serum urea and creatinine:
There was highly significant statistical difference as regards the
levels of serum urea and creatinine on comparing the three studied
groups. There was highly significant statistical increase in serum urea and
creatinine in group I (diabetics with nephropathy) when compared with
group II (diabetics without nephropathy) and with controls. There was no
significant statistical difference when group II (diabetics without
nephropathy) was compared with controls.
*As regards to the urinary ACR:
There was highly significant statistical difference as regards the
urinary ACR on comparing the three studied groups and highly
Summary and conclusion
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significant statistical increase in ACR in diabetics with nephropathy
(group I) when compared to diabetics without nephropathy (group II).
There was also highly significant statistical difference when group I was
compared with controls (group III). However there was no significant
statistical increase in ACR in group II in comparison to group III.
*As regards to the serum total cholesterol:
There was highly significant statistical difference as regards the level
of serum total cholesterol on comparing the three studied groups and
highly significant statistical elevation of serum total cholesterol in
diabetics with nephropathy when compared with diabetics without
nephropathy. There was also highly significant statistical difference when
each diabetic group was compared with controls.
*As regards to the genotyping of the HSP70-2 +1267 A/G
polymorphism by PCRLRFLP technique:
There was highly significant statistical difference as regards
genotype and allele distribution of HSP70-2 +1267 A/G polymorphism
among the three studied groups. There was highly significant statistical
increase in number and percentage of AA genotype and A allele
distribution in group II when compared to group I and also in group III
when compared to group I, while there was no significant difference
between group II and group III.
As regarding AG and GG genotypes and G allele, there was highly
significant increase of AG and GG genotypes and G allele in group I
when compared to group II and group III, while there was no significant
difference in group II when compared to group III.