A search for association between the polymorphic markers of PON1 and PON2 genes and diabetic nephropathy in patients with type I diabetes mellitus

Alleles and genotypes of polymorphic markers of paraoxonase 1 and paraoxonase 2 genes (PON1 and PON2) encoding enzymes of the body antioxidative defense were compared in type 1 diabetes mellitus patients with or without diabetic nephropathy. The patients with nonoverlapping ("polar") phenotypes constituted different groups. The first group contained patients with diabetic nephropathy (DN+, n = 62), clinical proteinuria (albuminuria above 300 mg per day), and at least 15-year disease duration. In control group, the patients had no diabetic nephropathy (DN-, n = 68), their albuminuria was below 200 mg per day, and disease duration was at least 20 years. Comparative analysis with exact Fisher's test revealed no significant differences in frequencies of alleles and genotypes of the PON1 gene polymorphic marker Gln192Arg and of PON2 gene polymorphic markers Ala148Gly and Cys311Ser. Our results suggest that the polymorphic markers studied are not associated with diabetic nephropathy among Russian patients in Moscow.     

Methods of genome engineering: a new era of molecular biology

Genome sequencing now progressing much faster than our understanding of the majority of gene functions. Studies of physiological functions of various genes would not be possible without the ability to manipulate the genome. Methods of genome engineering can now be used to inactivate a gene to study consequences, introduce heterologous genes into the genome for scientific and biotechnology applications, create genes coding for fusion proteins to study gene expression, protein localization, and molecular interactions, and to develop animal models of human diseases to find appropriate treatment. Finally, genome engineering might present the possibility to cure hereditary diseases. In this review, we discuss and compare the most important methods for gene inactivation and editing, as well as methods for incorporation of heterologous genes into the genome.     

Identification of the Locus Associated with Diabetic Nephropathy in Type 1 Diabetes Mellitus

Polymorphic tetranucleotide microsatellites D3S1512, D3S1744, D3S1550, and D3S2326 were used to study the association of chromosome region 3q21–q25 neighboring the angiotensin II receptor type 1 gene (AT ₂ R1) with diabetic nephropathy (DN) in diabetes mellitus type 1 (DM1). Allele and genotype frequencies were compared for DM1 patients with (N = 39) or without (N = 62) DN. Fisher's exact test with Bonferroni's correction revealed significant differences in frequencies of two D3S2326 alleles, one D3S1512 allele, and one allele and one genotype of D3S1550. No significant difference was observed with D3S1744. Thus, region 3q21–q25 proved tightly associated with DN in ethnic Russians with DM1 from Moscow.     

Polymorphic Gene Markers of Lipid Metabolism Are Associated with Diabetic Nephropathy in Patients with Type 1 Diabetes Mellitus

In groups of type 1 diabetes mellitus patients with and without clinical signs of diabetic nephropathy (n = 62 and 68, respectively), a search was made for associations between diabetic nephropathy and the polymorphic marker ε2/ε3/ε4 of apolipoprotein E gene (APOE), I/D marker of apolipoprotein B gene (APOB), and Ser447Ter marker of lipoprotein lipase-encoding gene (LPL). The risk of diabetic nephropathy was higher in the carriers of allele ε3 and genotype ε3/ε3 of the polymorphic marker ε2/ε 3/ε4 of APOE gene as well as in the carriers of allele I and APOB genotype I/I gene (OR = 2.08 and 2.16; 1.91 and 2.11, respectively). Conversely, the carriers of allele D showed a reduced risk of this complication (OR = 0.52). No significant differences in distribution of alleles and genotypes of the polymorphic marker Ser447Ter of LPL gene were found between the groups. Our results indicate that the genes encoding two major components of lipid metabolism are involved in the development of diabetic nephropathy in patients with type 1 diabetes mellitus.__________Translated from Genetika, Vol. 41, No. 7, 2005, pp. 931–937.Original Russian Text Copyright © 2005 by Yakunina, Shestakova, Voron’ko, Vikulova, Savost’yanov, Chugunova, Shamkhalova, Dedov, Nosikov.     

Polymorphism of gene encoding vascular angiotensin II receptor and microangiopathies in patients with insulin-dependent diabetes mellitus

Polymorphism A1166C of the AT1R gene encoding angiotensin vascular receptor [replacement of C (cytosine) for A (adenine)) at position 1166] was compared in patients with insulin-dependent diabetes mellitus (IDDM) complicated by diabetic nephropathy (DN) and in noncomplicated patients (n = 27 and n = 41, respectively) and also in patients with IDDM complicated by diabetic retinopathy (DR) and in correspondent noncomplicated individuals (n = 30 and n = 44, respectively). The frequency of AT1R gene alleles and genotypes in patients with IDDM complicated by DN did not differ significantly from that observed in patients with noncomplicated IDDM. In contrast, in patients with IDDM complicated by retinopathy, a significant decrease in the content of A allele (68.3% against 82.6%) and a significant increase in the content of C allele (31.7% against 17.4%) was found as compared with the control group. Thus, in the Moscow population, A1166C polymorphism of the AT1R gene is not associated with diabetic renal complications but indeed associated with diabetic retinal complications. C allele is a risk factor of DR (the relative risk, RR, is equal to 2.17), and A allele is, in contrast, a protective factor against early retinopathy development (RR is equal to 0.49).     

Pharmacokinetic study of rifampicin in the body of pregnant animals]

The study on distribution of 14C-rifampicin administered intramuscularly to pregnent animals showed that its concentrations in the blood, liver, kidneys, lungs and other organs did not practically change from those in nonpregnant animals. The concentration of 14C-rifampicin in the fetus organs was much lower than that in the organs of the adult animals. The liver and kidneys of the pregnant animals, as well as the fetus though to a less extent had a capacity for metabolism of 14C-rifampicin. The following products of biotransformation were detected: N-oxide of rifampicin, 25-deacetylrifampicin, 3-formylrifamycin SV and rifamycin SV.     

A Search for Association between the Polymorphic Markers of <Emphasis Type="Italic">PON1</Emphasis> and <Emphasis Type="Italic">PON2</Emphasis> Genes and Diabetic Nephropathy in Patients with Type I Diabetes Mellitus

Alleles and genotypes of polymorphic markers of paraoxonase 1 and paraoxonase 2 genes (PON1 and PON2) encoding enzymes of the organism antioxidant defense were compared in type 1 diabetes mellitus patients with or without diabetic nephropathy. The patients with nonoverlapping (“polar”) phenotypes constituted different groups. The first group contained patients with diabetic nephropathy (DN+, n = 62), clinical proteinuria (albuminuria above 300 mg per day), and at least 15-year disease duration. In control group, the patients had no diabetic nephropathy (DN−, n = 68), their albuminuria was below 200 mg per day, and disease duration was at least 20 years. Comparative analysis with exact Fisher’s test revealed no significant differences in frequencies of alleles and genotypes of the PON1 gene polymorphic marker Gln192Arg and of PON2 gene polymorphic markers Ala148Gly and Cys311Ser. Our results suggest that the polymorphic markers studied are not associated with diabetic nephropathy among Russian patients in Moscow.__________Translated from Genetika, Vol. 41, No. 6, 2005, pp. 844–849.Original Russian Text Copyright © 2005 by Voron’ko, Yakunina, Shestakova, Zotova, Chugunova, Shamkhalova, Vikulova, Debabov, Dedov, Nosikov.     

Identification of the locus associated with diabetic nephropathy in type 1 diabetes mellitus

Polymorphic tetranucleotide microsatellites D3S1512, D3S1744, D3S1550, and D3S232 were used to study the association of chromosome region 3q21-q25 neighboring the angiotensin II receptor type 1 gene (AT2R1) with diabetic nephropathy (DN) in diabetes mellitus type 1 (DM1). Allele and genotype frequencies were compared for DM1 patients with (N = 39) or without (N = 62) DN. Fisher's exact test with Bonferroni's correction revealed significant differences in frequencies of two D3S2326 alleles, one D3S1512 allele, and one allele and one genotype of D3S1550. No significant difference was observed with D3S1744. Thus, region 3q21-q25 proved tightly associated with DN in ethnic Russians with DM1 from Moscow.