The Frequency of Alleles of the Pro12Ala Polymorphism in PPARγ2 Is Different between Healthy Controls and
Patients with Type 2 Diabetes
D. PINTÉROVÁ, M. ČERNÁ, K. KOLOŠTOVÁ, P. NOVOTA, M. ČIMBUROVÁ, M. ROMŽOVÁ,
A. KUBĚNA, M. ANDĚL
The aim of this initial case-control study was to determine the association between common Pro12Ala polymorphism in the PPARγ2
gene and type 2 diabetes in the Czech Republic. Furthermore, the effect of this polymorphism on phenotypic characteristics and on levels
of lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides) was studied. One hundred thirty-three patients with
type 2 diabetes and 97 control subjects were investigated. PCR and restriction fragment length polymorphism (RFLP) analysis were
used for identification of individual genotypes. In the group of patients, three samples (2.26%) were identified as homozygous for the Ala/Ala
genotype and 99 samples (74.44%) were homozygotes for the Pro/Pro genotype. Thirty-one samples (23.31%) were identified as
Pro12Ala heterozygous. In the control group, six samples (6.19%) were homozygous for the Ala/Ala genotype and 61 samples (62.89%)
were homozygotes for the Pro/Pro genotype. Thirty samples (30.93%) were identified as Pro12Ala heterozygous. The allele frequency
for the Ala allele was lower in the type 2 diabetic group than in the control group (13.91% vs. 21.43%, P = 0.022). There was no
difference (at P < 0.05) between the phenotypic characteristics (BMI, sex) studied in the group of patients according to the Pro12Ala
genotype. There was no significant effect of the Pro12Ala polymorphism on lipid levels.
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The PPARGC1gene has been implicated in the regulation of several genes controlling energy metabolism. The prevalent
Gly482Ser polymorphism of the PPARGC1 gene has been shown to be associated with type 2 diabetes in some but not all studies.
The aim of this study was to analyse whether the Gly482Ser variant is a risk factor for development of type 2 diabetes in Slovene
population (Caucasians). Genotyping of the Gly482Ser polymorphism was performed for 545 subjects: 305 patients with type 2
diabetes and 240 non-diabetic controls. The Gly482Ser genotype distribution in patients with type 2 diabetes (AA = 11.5 %, AG = 42.3 %,
GG = 46.2 %) differed from genotype distribution in non-diabetic controls (AA = 6.3 %, AG = 46.3 %, GG = 47.5 %), and
the AA genotype was associated with 1.9-times increased risk of type 2 diabetes (95 % confidence interval 1.0–3.6; P = 0.036).
In conclusion, we suggest that the AA genotype of the Gly482Ser polymorphism of the PPARGC1 gene should be considered as
a risk factor for the development of type 2 diabetes in Caucasians.
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Melanocytes express MITF, which is crucial for the development of the melanocyte lineage and is overexpressed in malignant melanomas. Adenoviral E1A protein-expressing melanocytes are unpigmented, with the expression of MITF being silenced. We tested here a direct repression of the melanocyte-specific MITF promoter by E1A and its mutants. We found that the extreme N-terminus and conserved
region 1 are required for repression. In contrast, the motif in conserved region 2 (a.a. 122–126), as well as amino acids 26–35 at the N-terminus, are not necessary. As these two later motifs mediate E1A binding to the retinoblastoma protein or to the transcriptional
coactivator TRRAP, respectively, and are important for transformation by E1A in cooperation with other oncogenes, the results suggest
that the transformation-defective E1A can still efficiently repress the MITF promoter. The CREB binding motif-mutated promoter had lower activity, but was also repressed by the same E1A mutants in human melanoma cells. The E1A protein is known to also exert an antitumour activity, which is associated with its transcription repression function and the ability to induce apoptosis, and is a potential antimelanoma agent. Since recent data suggest that MITF may be a survival factor for melanoma cells, the E1A mutants described here might constitute a good targeting agent for antimelanoma therapy.
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Syngeneic, allogeneic and xenogeneic (rat) freshly isolated bone marow cells + stromal cell cultures maintained in vitro for 10–30 days,
as well as non-adherent cells removed from these cultures on 3rd–4th day were injected into the kidney parenchyma of mice,
immunosuppressed with hydrocortisone. In syngeneic grafts the immunosuppression was omitted. In all transplant systems bone tissue was formed inside the kidney with 20% to 32% variation. Bone produced by allogeneic and xenogeneic cells is subject to rejection when immunosuppression ceases, as the bone formed is of donor origin. The „floating” cells, regardless of the transplant system, normally discarded during media replacement, turned out to be efficient bone producers. This notion is of practical implication when bone marrow cells are
used for bone healing.
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