Dissertation/Thesis Abstract

DNA Variation in FOXP3 and DRD2 and Its Association with C-Reactive Protein
by Miller, Kimberly Nicole, M.S., Howard University, 2012, 76; 1529455
Abstract (Summary)

There has been a paucity of research on exposure to genetic risk factors and substance abuse/ use in African Americans. However, some studies have shown that drug use and abuse increases in African American adolescence. Substance use and abuse can be the result of multiple factors including environmental and social stressors ranging from high pressured jobs and financial problems to illicit drug use and violence in the community. These social stressors can suppress immune function and lead to increased risk of HIV/AIDS. Substance abuse continues to be one of society's most complex and prevalent problems. Over the past decade, research in the field of Psychoneuroimmunology, have explored the interaction between the brain and the immune system and its influence on one's health. This interaction can only be seen through the known biological links between the nervous system and the immune system.

Genome wide association studies have used approaches that involve rapidly scanning markers across complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. Better strategies to detect, treat and prevent diseases can now be developed using information from the genetic associations identified. The genes in this study are forkhead box P3 (FOXP3) and dopamine D2 receptor (DRD2). FOXP3 is an important gene responsible for regulating T regulatory cells in the immune system and suppressing the immune system in times of autoimmunity. DRD2 gene codes for the D2 receptor that binds dopamine and is involved in regulation of the central nervous system. The regulation of dopamine in the brain has been associated with a number of behavioral processes and the reward pathway involved in nicotine addiction.

Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used as methods to genotype the DRD2 rs1800497 SNP and the FOXP3 rs11465465 SNP in a sample population of 443 young African American adults from two urban communities in Washington, D.C. Distribution of allele and genotype frequencies for both SNPs were determined and compared between the study sample population and different HapMap populations in published data. The study population was comparable to populations of African descent with allele frequencies that were similar in both the DRD2 and Foxp3 SNPs involved in this study. The G allele was the only allele present in the DRD2 SNP among the CEU, HCB, JPT, and CEPH populations whereas, the two populations of African descent showed polymorphism. This study also investigated the association between genetic variation in FOXP3 and DRD2 with C-reactive protein (CRP). As a serum protein, CRP is found in the blood and is a biological marker of inflammation in the body. Inflammation is a hallmark of innate immunity. Increased levels of CRP occur with trauma, infection, and autoimmune disorders such as multiple sclerosis and lupus. The results in this study, indicated that polymorphisms in DRD2 was not associated with increased levels of CRP. However, polymorphisms in FOXP3 were associated with increased levels of CRP when adjusted for age. This study was the first to analyze the distribution of the rs11465465 SNP allele and genotype frequencies in the African American population and to evaluate the association of the rs11465465 SNP with CRP, a marker of inflammation.

Indexing (document details)
Advisor: Lee, Clarence M., Abbas, Muneer M.
Commitee: Abbas, Muneer M., Ampy, Franklin A., Dunston, Georgia M., Lee, Clarence M.
School: Howard University
Department: Biology
School Location: United States -- District of Columbia
Source: MAI 51/03M(E), Masters Abstracts International
Subjects: African American Studies, Black studies, Genetics, Immunology
Keywords: C-reactive protein, DRD2, FOXP3, Genetic variation
Publication Number: 1529455
ISBN: 9781267729149