Sandra O'Dell

1. Effect of diet-gene interaction on lipid profile and insulin sensitivity in large intervention studies (in collaboration with Prof Tom Sanders). <p>Recently my main focus has been the peroxisome proliferator-activated receptor genes, PPAR&alpha; and PPAR&gamma; and the PPAR&gamma; target gene adiponectin. We have explored the effect of dietary fatty acid interaction with PPARG and PPARA variants on plasma lipids in the RISCK study, a randomised control trial in which a high SFA diet was replaced by MUFA or carbohydrate. We found significant diet x ADIPOQ gene x age interaction in determination of serum adiponectin. Habitual dietary P:S ratio x PPARG gene interaction and dietary fat x PPARA and PPARG gene interaction in determination of plasma lipids has also been shown. Ongoing investigations are centred on gene x diet interactions on lipid profiles and vascular properties related to n3-PUFA intake in the MARINA study.</p> <p><br />2. PPAR&gamma; function in mitigation of lipodystrophic effects of anti-retroviral therapy (in collaboration with Dr Anne Mullen).</p> <p>The use of anti-retroviral therapy can lead to HIV-associated lipodystrophy syndrome (HALS). There is some evidence that the activity of PPAR&gamma; is down-regulated by anti-retroviral drugs. Pharmacological PPAR&gamma; ligands such as rosiglitazone, have shown positive effects on HALS in some RCTs. We aim to investigate whether pre-treatment of cultured adipocytes with PUFAs alters the level of activated PPAR&gamma; extracted from cells exposed to anti-retrovirals. Promising results in vitro are expected to lead to human trials.</p> <p><br />3. Functional and genomic changes following activation of TRPA1 receptors in the normal and hypertensive peripheral vasculature (in collaboration with Prof Sue Brain, Cardiovascular Sciences).</p> <p>Research in mouse transcriptomics was initiated in an attempt to identify new players in energy regulation and obesity susceptibility. We originally investigated differential expression of hypothalamic genes in the dietary-induced obesity model C57BL6 mouse on high-fat and standard diets, using microarrays. The aim of our current collaboration is to determine how activation of peripheral vascular responses by transient receptor potential (TRP) ankyrin 1 (TRPA1) influences blood flow in the normal and angiotensin-II mouse model of hypertension to investigate the molecular and genetic changes that occur before and after activation of TRPA1 in the ear vasculature. We aim to identify genes and pathways that are affected by hypertension and/or exhibit selective altered expression following stimulation and are linked to the TRPA1 neurogenic peripheral responses in hypertension. Possible functional analysis in vivo will involve WT and TRPA1KO mice.</p> <p>&nbsp;</p> <p>Recent publications</p> <p>AlSaleh A, O'Dell SD, Frost GS, Griffin BA, Lovegrove JA, Jebb SA, Sanders TA (2011) Single nucleotide polymorphisms at the ADIPOQ gene locus interact with age and dietary intake of fat to determine serum adiponectin in subjects at risk of the metabolic syndrome. Am J Clin Nutr 94:1-8.</p> <p><br />Lee AK, Kyriakou T, Weston AJ, O'Dell SD (2010) Functional single nucleotide polymorphism in acetyl-CoA carboxylase ACACB gene promoter. DNA Cell Biol 29:703-12.</p> <p><br />Lee AK, Mojtahed-Jaberi M, Kyriakou T, Aldecoa-Otalora Astarloa E, Arno M, Marshall NJ, Brain SD, O'Dell SD (2010) Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus. Nutrition 26: 411-422.</p> <p><br />Liu G, Riese H, Spector TD, O'Dell SD, Stolk R, Snieder H (2009). Bivariate genetic modeling of the response to an oral glucose tolerance challenge: A gene-environment interaction approach. Diabetologia 52:1048-1055.</p> <p><br />Goyenechea E, Collins LJ , Parra D, Abete I, Crujeiras AB, O'Dell SD, Alfredo Mart&iacute;nez J. (2009) The -11391 G/A polymorphism of the adiponectin gene promoter is associated with metabolic syndrome traits and the outcome of an energy-restricted diet in obese subjects. Horm Metab Res 41:55-61.</p> <p><br />Goyenechea E, Collins LJ , Parra D, Liu G, Snieder H, Swaminathan R, Spector TD, Alfredo Mart&iacute;nez J, O'Dell SD (2008) CD36 gene promoter polymorphisms are associated with low density lipoprotein-cholesterol in normal twins and after a low-calorie diet in obese subjects. Twin Res Hum Genet 11:621-628.</p> <p><br />Kyriakou T, Collins LJ, Spencer-Jones NJ, Malcolm C, Wang X, Snieder H, Swaminathan R, Hart DJ, Spector TD, O'Dell SD (2008) Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity. J Hum Genet 53:718-727.</p> <p><br />Ge D, Gooljar SB, Kyriakou T, Collins LJ, Swaminathan R, Snieder H, Spector TD, O'Dell SD (2008) Association of common JAK2 variants with body fat, insulin sensitivity and lipid profile. Obesity (Silver Spring)16:492-449.</p> <p><br />Snieder S, Wang X, Shiri-Sverdlov R, van Vliet- Ostaptchouk JV, Hofker MH, Spector TD, O'Dell SD (2008) Associations with general and central obesity in post-menopausal women confirm TUB as a candidate gene for late-onset obesity in humans. Diabetologia 51:54-61.</p>

Nutrigenetic interaction in the development of metabolic syndrome traits.