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Polymorphisms in the IL-12 and IL-12R Genes: Altering Plasmodium Falciparum Disease Outcome

Strong, LaToya Michelle (2009) Polymorphisms in the IL-12 and IL-12R Genes: Altering Plasmodium Falciparum Disease Outcome. Master's Thesis, University of Pittsburgh. (Unpublished)

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Malaria is a major public health concern as greater than 40% of the world's population is at risk. Globally and annually, there are approximately 300-500 million incident cases a year resulting in between 1 and 2 million deaths; the majority of these deaths occur in children under the age of 5 and in pregnant women. There are several disease complications that can arise from malaria, two of which are high density parasitemia (HDP) and severe malaria anemia (SMA). Not everyone who gets malaria gets HDP or SMA, and the underlying reason for this is unknown, however, research has shown that innate immune mediators, including Interleukin-12 (IL-12), play an important role. Currently there is no vaccine for malaria and drug resistance is a major issue. This study is of public health significance because it can give insight into the difference between those individuals who progress to severe disease complications and those that do not; potentially giving rise to novel drug and vaccine development. The severity and occurrences of these complications vary by age, region, and level of malaria endemicity. Previous studies have indicated a role for not only circulating levels of IL-12, but also for polymorphisms in the IL-12 and Interleukin-12 Receptor (IL-12R) genes. To gain a better understanding of the role that polymorphisms in the IL-12 and IL-12R genes may have we conducted a case-control study to compare phenotypic data to genotypic data. We investigated four Single Nucleotide Polymorphisms (SNPs) - rs2243113, rs2243140, rs383483 and rs429774 - in the IL-12 and IL-12R genes to determine if a correlation existed between disease status and genotype. We found that for all four SNPs, there was not a correlation between disease status and genotype. We also investigated the distribution of these four SNPs across populations with varying malaria endemicity. We also found that in all of the populations except for the Kenyan population there is a higher frequency of homozygous wildtype alleles for both rs2243113 and rs2243140 and a higher frequency of heterozygotes for rs383483.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Strong, LaToya
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMartinson, Jeremyjmartins@pitt.eduJMARTINS
Committee MemberHartman, Amyhartman2@pitt.eduHARTMAN2
Committee MemberFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Date: 29 September 2009
Date Type: Completion
Defense Date: 27 July 2009
Approval Date: 29 September 2009
Submission Date: 10 June 2009
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: interleukin-12; malaria; single nucleotide polymorphisms
Other ID:, etd-06102009-232115
Date Deposited: 10 Nov 2011 19:46
Last Modified: 15 Nov 2016 13:44


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