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The RNA interference pathway (RNAi) is a specific and powerful biological process, triggered by small non-coding RNA molecules and involved in gene expression regulation. In this work, we explored the possibility of increasing the biological stability of these RNA molecules by replacing their natural ribose ring with an acyclic L-threoninol backbone. In particular, this modification has been incorporated at certain positions of the oligonucleotide strands and its effects on the biological properties of the siRNA have been evaluated. In vitro cellular RNAi assays have demonstrated that the L-threoninol backbone is well tolerated by the RNAi machinery in both double and single-stranded fashion, with activities significantly higher than those evinced by the unmodified RNAs and comparable to the well-known phosphorothioate modification. Additionally, this modification conferred extremely strong resistance to serum and 3′/5′-exonucleases. In view of these results, we applied this modification to the knockdown of a therapeutically relevant human gene such as apolipoprotein B ( ApoB). Further studies on the activation of the innate immune system showed that L-threoninol-modified RNAs are slightly less stimulatory than unmodified RNAs.

We have analyzed allele frequency distribution at the hypervariable locus 3 to the apolipoprotein B gene in a healthy population sample (241 women and 246 men) from the Belgrade area. The bimodal distribution of sixteen different hypervariable region (HVR) alleles and the heterozygosity index (average 0.76) in both samples are similar to ones reported for other Caucasian populations. However, we found the hypervariable element containing 34 repeats-HVE34 allele to be the most common one in both female and male samples, and that there was a lower frequency of the HVE GT 36 alleles. For further analysis of 3HVR allele frequency and its possible association with serum lipid levels, all HVR alleles were grouped into five main types (HVE LT 32, HVE32, HVE34, HVE36, and HVE GT 36), and the samples were divided into lipid quartiles. We found that (1) apo B gene 3HVR polymorphism is associated with variation of normal lipid levels in males, (2) HVE32 alleles are associated with decreased serum levels of total cholesterol, LDL cholesterol, and triglycerides, and (3) HVR genotypes containing HVE34 and HVE36 alleles are associated with elevated serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides. (C) 1998 Wiley-Liss, Inc.

We have analyzed allele frequency distribution at the hypervariable locus 3 to the apolipoprotein B gene in a healthy population sample (241 women and 246 men) from the Belgrade area. The bimodal distribution of sixteen different hypervariable region (HVR) alleles and the heterozygosity index (average 0.76) in both samples are similar to ones reported for other Caucasian populations. However, we found the hypervariable element containing 34 repeats-HVE34 allele to be the most common one in both female and male samples, and that there was a lower frequency of the HVE GT 36 alleles. For further analysis of 3HVR allele frequency and its possible association with serum lipid levels, all HVR alleles were grouped into five main types (HVE LT 32, HVE32, HVE34, HVE36, and HVE GT 36), and the samples were divided into lipid quartiles. We found that (1) apo B gene 3HVR polymorphism is associated with variation of normal lipid levels in males, (2) HVE32 alleles are associated with decreased serum levels of total cholesterol, LDL cholesterol, and triglycerides, and (3) HVR genotypes containing HVE34 and HVE36 alleles are associated with elevated serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides. (C) 1998 Wiley-Liss, Inc.

The apolipoprotein B (apoB) signal peptide polymorphism was studied in unrelated healthy individuals. A total of 232 women and 222 men were analyzed separately. The relative frequencies of Del allele in women and men were 0.42 and 0.37, respectively. More heterozygous individuals were detected in comparison with other populations, using a modified silver staining method on polyacrylamide gel for visualization of Ins and Del alleles. There was no statistically significant difference in mean lipid levels adjusted for age, BMI, smoking habit and blood pressure between the three Ins/Del genotypes in both samples (ANOVA). Therefore, no differences were shown in the genotype frequency distribution throughout the lipid quartiles. (C) 1997 Elsevier Science B.V.

The apolipoprotein B (apoB) signal peptide polymorphism was studied in unrelated healthy individuals. A total of 232 women and 222 men were analyzed separately. The relative frequencies of Del allele in women and men were 0.42 and 0.37, respectively. More heterozygous individuals were detected in comparison with other populations, using a modified silver staining method on polyacrylamide gel for visualization of Ins and Del alleles. There was no statistically significant difference in mean lipid levels adjusted for age, BMI, smoking habit and blood pressure between the three Ins/Del genotypes in both samples (ANOVA). Therefore, no differences were shown in the genotype frequency distribution throughout the lipid quartiles. (C) 1997 Elsevier Science B.V.

The apolipoprotein B (apoB) signal peptide polymorphism was studied in unrelated healthy individuals. A total of 232 women and 222 men were analyzed separately. The relative frequencies of Del allele in women and men were 0.42 and 0.37, respectively. More heterozygous individuals were detected in comparison with other populations, using a modified silver staining method on polyacrylamide gel for visualization of Ins and Del alleles. There was no statistically significant difference in mean lipid levels adjusted for age, BMI, smoking habit and blood pressure between the three Ins/Del genotypes in both samples (ANOVA). Therefore, no differences were shown in the genotype frequency distribution throughout the lipid quartiles. (C) 1997 Elsevier Science B.V.