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of the nitric oxide synthase (NOS) enzymes responsi- and the risk of DPN .
ble for NO synthesis. Endothelium derived NO plays
a key role in the regulation of vascular tone and has GENETIC VARIANTS OF DPN IN DIFFERENT
vaso-protective effects by removing superoxide radi- ETHNIC POPULATIONS
cals and suppressing platelet aggregation, leukocyte
adhesion, and smooth muscle cell proliferation. How- Up-to-date there were only few ethnic groups have
ever, dysfunctional endothelial nitric-oxide synthase described population specific genetic variants as-
(eNOS) might play a critical role in the pathogenic sociated with DPN. In a study conducted by Lu et
pathway leading to diabetic vascular complications al., 2017, ten SNVs associated with pathogenesis of
including DNP. Therefore, eNOS is considered as a T2DM were studied and they identified rs5219 on
candidate for the progression of DPN. KCNJ11 (E23K) gene is significantly associated with
peripheral nerve function in a Chinese population
In the early stages of DPN, abnormalities in the vasa with T2D [24]. Jia Y, Tong and Min L., 2015, studied
nervorum and loss of nerve fibers can be seen in as- the significance of functional GRP78 gene variants
sociation with hyperglycemia. Damage to the nervous in predicting the onset of type 2 diabetic peripher-
tissue results in an increase intravascular endothelial al neuropathy in the Chinese population. This study
growth factor (VEGF) plasma levels in diabetic animal suggested that the GRP78 rs391957 promoter poly-
models . The ischemia and hypoxia in the nerves of morphism is a potential risk factor for type 2 diabetic
patients with T2D due to microangiopathy of vasa peripheral neuropathy in this population . Prasad et
nervorum has always been observed and may be a al., 2015, studied forty-two patients with T2D from
key pathogenic mechanism of DPN . An association the Institute of Diabetology, Madras Medical College
study by Ghisleni et al., 2015, showed a clear associa- and Rajiv Gandhi Government General Hospital in
tion between diabetic polyneuropathy and the C936T Chennai, Tamil Nadu, India. In this study, the extent
polymorphism of the VEGF gene and the C242T poly- of DNA damage in patients suffering from T2D, both
morphism of the p22phox allele of CYBA gene. with and without neuropathy was analyzed. No ge-
netic variants were evaluated in this study. The data
Functional GRP78 variants in heat shock protein
family A (Hsp70) member 5 (HSPA5) genes are like- demonstrated that the frequency of DNA damage
ly to have some influence on the gene expression, was significantly higher in the T2D patients with DPN
which results in the dysfunction of peripheral nerves than in the controls [60]. Stoian et al., 2015, conduct-
and neuropathy. According to Jia Y, Tong Y and Min ed a study in the University Center of TırguMures,
L, 2015, functional GRP78 rs391957 variants, which Romania. In their case control study, which included
are located in the promoter region 57168556T>C are a total of 182 participants, including 84 unrelated pa-
known to cause abnormal promoter activities signifi- tients with T2D and an age-matched control group
cantly associated with DPN . consisting of 98 unrelated individuals without T2D,
they evaluated the influence of GSTM1, GSTT1, and
Adiponectin gene (ADPN) serves as a protective fac- GSTP1 variants on T2D and DPN risk. Their data sug-
tor in preventing diabetes progression by suppress- gested that GSTM1, GSTT1 and GSTP1 gene variants
ing inflammatory responses and increasing insulin were not associated with individual susceptibility to
sensitivity . SNVs of ADPN may influence T2DM, developing DPN in patients with T2D in Romanian
but ADPN variants SNV45 (45T/G, rs2241766) and population .
SNV276 (276G/T, rs1501299) are the two most prom-
inent variants influencing the disease progression, An association study of C936T polymorphism of
specially pathogenesis of DPN . A case control study the VEGF gene and the C242T polymorphism of the
conducted by Ji et al., 2015, to evaluate the associa- p22phox gene with T2D and DPN in a population of
tion between ADPN gene variants and pathogenesis Caucasian ethnicity was studied by Ghisleni et al., in
of DPN in T2D patients indicated an increased risk 2015. According to their results, the C936T polymor-
of DPN in T2D patients, by down-regulating ADPN phism of the VEGF gene and C242T polymorphism
expression which resulted in significantly reduced of the p22phox gene did not correlate with the risk
circulating ADPN plasma levels. Furthermore, they of developing diabetes mellitus or neuropathic signs
reported that the polymorphism frequencies of GG and symptoms. When considering the results of oth-
and GT haplotypes in the DPN group were signifi- er studies, a substantial heterogeneity in the findings
cantly lower than the matched control group, while is observed, which demonstrates a complex link be-
the frequency of the TG haplotype in the DPN group tween the risk factors of DM, and genetic predispo-
was markedly higher than the control group, showing sition to DPN .
the clear association between ADPN gene variants

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