1. Serum Lipid Profile, Apolipoprotein E Genotype and Visceral Leishmaniasis Infection in a Northeastern Brazilian Population Adam P. Simons 1, Gloria R. Monteiro 2, Nubia N. Pontes 2, Taysa M. Feitosa 2, Upasna Gaur 3, Richard D. Pearson 4, Mary E. Wilson 3, Selma M. Jeronimo 2 1.University of California-Davis, Sacramento, CA, 2.Federal University of Rio Grande do Norte, Natal, Brazil, 3.University of Iowa, Iowa City, IA, 4.University of Virginia, Charlottesville, VA

2. Leishmania Lifecycle

3. Phenotypes: 1.No Current Infection (N) -Antibody Neg. 2.Acute Illness (VL) 3.Asymptomatic Infection (DTH+) -Antibody +/- ? Environmental and Host Factors Determine Response to Infection **Wiki commons

4. Cholesterol Augments Leishmania Infectivity Rodriguez, Gaur, Wilson 2006

5. Cohort of families in VL endemic Area in Natal, Brazil Family PairsNumber of Pairs Sibling-Sibling692 Parent-Offspring892 Grandparent-Grandchild268 Avuncular414 Cousin249

6. Serum Lipids by Phenotype

7. Cholesterol Level by Phenotype vs. Age

8. Acute VL Effects: ↓ TC, HDL ↓ ApoA, ApoB, ApoC ↑ TG ↑ ApoE Barral et al (1986) Bekaert et al (1992) Nieto (1992)

9. Inflammation  Dyslipidemia Parasitic Infection (leptospirosis) ↓ Total Cholesterol, HDL ↑ TG Bacterial infections: ↓ Total Cholesterol, HDL TNFa ↑ Hepatic TG ↓ Lipoprotein Lipase Grunfeld et al 1991 IL-6 ↑ LDL Rec. Expression Liberopoulous et al 2004 ApoE Dijk et al 1999

10. ApoE Genotype and Leishmaniasis? 109 families in Natal Linkage Analysis –Chr 9 (VL) –Chr 15 (DTH+) –Chr 19 (DTH+) Source: Jeronimo et al 2007 Apolipoprotein E Jerónimo Genome-Wide Scan 2007

11. ApoE Genotype Founders Genotype Counts Percent E2/E312.7 E2/E412.7 E3/E32259.5 E3/E41335.1 E4/E400.0 Allele Counts E222.7 E35878.4 E41418.9 VL FAMILIES Genotype Counts Percent E2/E3211.8 E2/E400.0 E3/E31058.8 E3/E4529.4 E4/E400.0 Allele Counts E225.9 E32779.4 E4514.7 CONTROL FAMILIES

12. Selective Pressure of ApoE Allele%Genotype% E28.32/21.4 E377.12/311.1 E414.63/358.3 2/42.8 3/426.4 4/40 n=72 children in Ceara Oriá et al (2005) Wiki commons

13. Future Directions Large-power study of ApoE genotype Lipid metabolic pathways in VL recovery –LXR, PPAR, Cholesterol Biosynthesis pathway gene expression across disease process.

14. Acknowledgments Mary E. Wilson, University of Iowa Richard D. Pearson, University of Virginia Noah Craft, University of California Edgar Carvalho, UFBA Cristina Otonis, UFRN Gloria Monteiro, UFRN Upasna Gaur, University of Iowa Selma Jerónimo, UFRN NIH, CNPq and UC Davis for financial support