Date of Award

January 2016

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Richard Bucala

Second Advisor

Peter J. Krause

Abstract

Background: TB is a leading cause of mortality, infecting over one-third of the world’s population. Difficulties combating the disease are compounded by the fact that a majority of TB infections remain in an asymptomatic latent state. Macrophage migration inhibitory factor (MIF) is an innate cytokine that is encoded in a functionally polymorphic genetic locus with characterized allelic variants that correlate to TB progression. Understanding the genetic factors that regulate host immune responses to TB will help to identify individuals who are at higher risk of severe infection.

Methods: A case-control study of HIV+ active pulmonary TB cases and HIV+ controls with no history of active TB was conducted on a South African cohort. With informed consent, we obtained demographics, clinical information, and blood samples for determination of MIF promoter polymorphisms: a functional -794 CATT5-8 microsatellite, and a closely associated -173 G/C SNP. Serum cytokine levels were quantified using ELISA.

Results: Among 165 enrolled patients (100 cases, 65 controls), 79 were female (40 cases, 39 controls). Aggregate polymorphism assessment revealed non-significant distribution differences between cases and controls for both the 794 CATT5-8 (p = 0.3316) and -173 G/C (p = 0.7452) loci. However, stratification by gender reveals a near significant difference in the frequency of CATT5/5 (p-value = 0.0863) and -173 G/G (p-value = 0.0949) low expresser genotypes in female cases versus controls but not in males. ELISA showed a significant difference (P = 0.0056) in serum cytokine levels between cases and controls but not between different polymorphisms.

Conclusions: The results from this study suggest that MIF polymorphisms might contribute to susceptibility to TB in a sex-dependent manner and that MIF low-expresser genotypes might confer higher risk for active TB. However, additional studies will need to be done to establish this relationship.

Comments

This is an Open Access Thesis.

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