Prenatal omega-3 fatty acid supplementation does not affect offspring telomere length and F2-isoprostanes at 12 years: A double blind, randomized controlled trial.

BACKGROUND: Oxidative stress and nutritional deficiency may influence the excessive shortening of the telomeric ends of chromosomes. It is known that stress exposure in intrauterine life can produce variations in telomere length (TL), thereby potentially setting up a long-term trajectory for disease susceptibility. OBJECTIVE: To assess the effect of omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy on telomere length and oxidative stress in offspring at birth and 12 years of age (12y). DESIGN: In a double-blind, placebo-controlled, parallel-group study, 98 pregnant atopic women were randomised to 4g/day of n-3 LCPUFA or control (olive oil [OO]), from 20 weeks gestation until delivery. Telomere length as a marker of cell senescence and plasma and urinary F2-isoprostanes as a marker of oxidative stress were measured in the offspring at birth and 12y. RESULTS: Maternal n-3 LCPUFA supplementation did not influence offspring telomere length at birth or at 12y with no changes over time. Telomere length was not associated with F2-isoprostanes or erythrocyte total n-3 fatty acids. Supplementation significantly reduced cord plasma F2-isoprostanes (P<0.001), with a difference in the change over time between groups (P=0.05). However, the differences were no longer apparent at 12y. Between-group differences for urinary F2-isoprostanes at birth and at 12y were non-significant with no changes over time. CONCLUSIONS: This study does not support the hypothesis that n-3 LCPUFA during pregnancy provides sustained effects on postnatal oxidative stress and telomere length as observed in the offspring.

Elevated plasma magnesium and calcium may be associated with shorter telomeres in older South Australian women.

Telomeres are structures that cap the ends of chromosomes. The integrity of the telomere structure and its DNA hexamer (TTAGGG)n repeat sequence is critical for protecting the ends of chromosomes from degradation and in maintaining overall chromosomal stability. Currently, there are limited data on the influence that nutrition has on telomere length. Recent studies have suggested that micronutrients may influence telomere length. Here we examined the relationship between telomere length in lymphocytes and plasma calcium, magnesium, selenium and zinc status in a healthy cohort of younger and older adults. We report a negative association between telomere length and both plasma calcium and magnesium levels, (r=-0.47, P=0.03 and r=-0.61, P=0.001 respectively), in older females; Intriguingly Ca/Mg ratio was positively associated with telomere length (r=0.55, P=0.007). These relationships were not observed in the younger adults, nor in the older males. In conclusion, our study provides preliminary evidence suggesting that levels of plasma magnesium and calcium may impact on telomere length in lymphocytes in older women.

Association of TNF-alpha-857C with inflammatory bowel disease in the Australian population.

BACKGROUND: It is now well established that susceptibility to inflammatory bowel disease is in part genetic, with one localization on chromosome 6 (IBD3) having been replicated in a number of populations. A candidate in that region, TNF-alpha, contains polymorphisms in the promoter region that appear to be associated with disease. METHODS: More than 600 individuals from 170 multiplex IBD families were genotyped for four polymorphisms in the TNF-alpha gene and analysed for association. RESULTS AND CONCLUSION: A strong association was observed between transmission of the -857 C allele and disease. This effect was strongest in those families in which the NOD2 risk alleles are also segregating, supporting the existence of an interaction between IBD3 and IBD1 on chromosome 16.

CARD15/NOD2 risk alleles in the development of Crohn's disease in the Australian population.

We have previously reported strong evidence for linkage between IBD1 and Crohn's disease (CD) in Australian Crohn's disease families. Three risk alleles for Crohn's disease, (Arg702Trp (C/T), Gly908Arg (G/C) and 980fs981 (-/C), were recently identified in the CARD15/NOD2 gene on chromosome 16, implicating this as the IBD1 locus. Using a novel diagnostic PCR-RFLP, we have examined the frequency of these alleles in 205 multiplex IBD families, 107 sporadic Crohn's disease cases and 409 normal individuals. We demonstrate that the three risk alleles are more frequent in Crohn's disease, than in controls, with allelic frequencies of 0.11, 0.02 and 0.07 respectively. Heterozygosity for individual variants conferred a three-fold increase in risk for Crohn's disease while substantially higher risks were associated with being homozygous or compound heterozygous. Despite a significantly lower population allele frequency for the frameshift mutation than reported by other groups, we see a similar contribution by this allele to the risk of developing Crohn's disease. While the three risk alleles influence susceptibility to Crohn's disease in Australia, we show that these alleles do not fully explain the linkage evidence and suggest that there are very likely additional IBD1 susceptibility alleles yet to be described in Australian CD at the NOD2 locus. We also show a second linkage peak in Australian CD that provides some support for a second disease susceptibility locus on chromosome 16.

Association of TNF-α-857C with Inflammatory Bowel Disease in the Australian Population.

BACKGROUND: It is now well established that susceptibility to inflammatory bowel disease is in part genetic, with one localization on chromosome 6 (IBD3) having been replicated in a number of populations. A candidate in that region, TNF-α, contains polymorphisms in the promoter region that appear to be associated with disease. METHODS: More than 600 individuals from 170 multiplex IBD families were genotyped for four polymorphisms in the TNF-α gene and analysed for association. RESULTS AND CONCLUSION: A strong association was observed between transmission of the -857 C allele and disease. This effect was strongest in those families in which the NOD2 risk alleles are also segregating, supporting the existence of an interaction between IBD3 and IBD1 on chromosome 16.