alexa Tuberculosis and Genetics of Sub-Saharan Africa Human Population | Open Access Journals
ISSN: 2161-1068
Mycobacterial Diseases
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Tuberculosis and Genetics of Sub-Saharan Africa Human Population

Gerald Mboowa1,2*

1Department of Medical Microbiology, College of Health Sciences, Makerere University, P.O Box 7072, Kampala, Uganda

2School of Allied Health Sciences, International Health Sciences University, P.O Box 7782, Kampala, Uganda

Corresponding Author:
Gerald Mboowa
School of Allied Health Sciences
International Health Sciences University
P.O Box 7782, Kampala, Uganda
Tel: +256712841790
E-mail: [email protected]

Received Date: May 16, 2014; Accepted Date: July 29, 2014; Published Date: August 05, 2014

Citation: Mboowa G (2014) Tuberculosis and Genetics of Sub-Saharan Africa Human Population. J Mycobac Dis 4:164. doi:10.4172/2161-1068.1000164

Copyright: © 2014 Mboowa G. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Mycobacterial Diseases


Sub-Saharan Africa has continued leading in the prevalence and incidence of tuberculosis (TB). The epidemiological triad of infectious diseases includes a susceptible host, pathogen/agent, and environment. Sub- Saharan Africa has the highest prevalence and incidence of TB. It is imperative that all aspects of vertices of the infectious disease triad are analysed to better understand why this is so. Many studies have been done to address this intriguing reality though these have mainly addressed pathogen and environmental components of the triad regarding TB infection. The host factors have not been exhaustively studied in this high TB burden region probably due to lack of the necessary expertise and technologies among African scholars yet three components of the triad interact to determine the disease outcome. Amongst host factors, genetic structure of the host greatly affects progression of disease following exposure. Studies have revealed that Africa is the most genetically diverse region of the world in addition to being the origin of modern humans therefore it would be important to study genetics of sub-Saharan African population in relation to TB. This review seeks to analyze contribution of host genetics to the observed variation in susceptibility to TB infection in this region.


Pulmonary tuberculosis; Infectious diseases; Triad; Genetic


TB: Tuberculosis, PTB: Pulmonary Tuberculosis, PMN: Polymorphonuclear Cells, IFN-γ: Interferon Gamma; IL: Interleukin


Tuberculosis (TB) continues to devastate sub-Saharan Africa populations, a region with a total of 27 countries. In 2012, African region had approximately one quarter of the world’s TB cases, and the highest rates of cases and deaths relative to population (255 incident cases per 100,000 on average, more than double the global average of 122). However, sub-Saharan Africa carried the greatest proportion of new cases per population with over 255 cases per 100,000 population [1]. Africa is thought to be the ancestral homeland of all modern humans, and is the more recent homeland of millions of individuals whose ancestors were brought to Europe and to the Americas as slaves [2]. There is much to learn from the genetics of sub-Saharan African populations regarding human origins, evolution as well as origin and nature of complex human diseases. At present, we have little understanding of the genetic structure of sub-Saharan populations and the genetic basis of complex disease in African populations because very few genetic studies have been conducted in African ethnic groups [2]. Research activity has traditionally been biased towards the study of non-African populations, and our knowledge of even the most fundamental information about the genetic basis of disease in Africa is quite limited [2].

Iam compelled to propose that modern humans who migrated away from sub-Saharan Africa encountered new environment and exotic pathogens in areas where they settled. We now know that infectious diseases have and will continue shaping the course of evolution of human species .In this antibiotic era, we should accept that drugs will equally act as a strong selective pressure on the human genome therefore the modern humans are under two important selective forces. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity [3]. Disease outcome is multifactorial process, requiring interplay of host-environment-microbial factors ultimately determine disease susceptibility. Genetic structures of the exposed human populations will determine the susceptibility patterns that are always observed in the herd population. Recent genome- wide analysis indicate that among the diverse environmental factors that most likely acted as selective pressures during the evolution of human species (climate, diet regimes, and infections), pathogen load had the strongest influence on the shaping of human genetic variability [4]. Possibly the indigenous pathogens in sub-Saharan Africa co-evolved with their hosts creating unique genetic profiles in these human populations. I propose that a form of Newton’s third law of motion happens during an interaction between host and pathogen; action and reaction is equal and opposite.

This infers that there is a selective pressure exerted by these pathogens onto selected host genes and in response specific pathogen genes received similar pressure from the host driving host/pathogen diversity observed as unique genetic profiles in both host and pathogen accounting for co-evolution. I further propose that these unique genetic profiles created over time affect vaccine efficacy and of late we know that treatment outcome is also affected by the host genetic structures therefore these genetic variation will in future undermine use of universal vaccines and drugs. The unique genetic profiles created in these human populations can act as risk genetic factors for emerging pathogens.

Human host genetic diversity and infectious diseases

The high levels of genetic diversity in African populations and their demographic history make these populations particularly informative for the fine mapping of complex genetic diseases [5] as well as known complex infectious and emerging diseases. Studies using human mitochondrial DNA and nuclear DNA markers consistently indicate that Africa is the most genetically diverse region of the world [6]. Historically, human population genetic studies have relied on one or two African populations as being representative of African diversity, but recent studies show extensive genetic variation among even geographically close African populations, which indicates that there is not a single ‘representative’ African population [3]. TB was introduced in Africa by probably early settlers, sailors, colonialists, missionaries and traders. The environment in this region plus the TB naïve host genetic structures of the region may have account for the rapid spread of the disease. Studies now indicate that different strains of TB have geographical preferences.

The immunological responses to MTB are due to the interaction between the human host immune system (host genetics), bacterial and environmental factors [7]. Genetics as well as acquired defects in host immune response pathways greatly increase the risk of progressive disease [8]. Furthermore, host genetics is inherent and relatively constant for an individual but acquired defects may arise from mainly the environment and antibiotic use. Results from genome wide linkage studies suggest that TB disease susceptibility is highly likely to be polygenic, with contributions from many minor loci [9] and a large number of TB susceptibility markers have been identified from candidate gene studies as ‘disease-causing’ genes which include TIRAP, HLA DQB1, VDR, IL-12β, IL12Rβ1, IFN-γ, SLC11A1 and MCP- 1. However, to date the greatest evidence to support an underlying genetic basis for TB has come from the discovery of single gene defects predisposing to disseminated and often lethal mycobacterial disease [10]. I can assert that the indigenous infections like malaria created unique genetic structures in these mixed ethnic populations which can be risk factors for exotic infectious diseases like tuberculosis, HIV/AIDS and other emerging diseases. A notion that exposure to indigenous pathogens/parasites in these areas shaped the genetic structures of these native human populations resulting in the observed inter-ethnic disparities in susceptibility to new infectious agents is undisputable.

Tuberculosis susceptibility genes in sub-Saharan Africa population

A lot of attention has been given to study the importance of the Mycobacterium tuberculosis (MTB) pathogen and the genetic constitution of the host largely ignored especially in the most affected regions like sub-Saharan Africa. It is estimated that only 10% of those who become infected with TB will ever develop clinical disease [11]. A growing body of evidence suggests that host genetics play a role in the predisposition to TB disease, in addition to pathogen, environmental, and socioeconomic factors [12,13]. Genetic factors contributing to TB susceptibility include variants of the human leukocyte antigen (HLA) class II complex [14-17] and the vitamin D receptor gene (VDR) [18-21] among others. HLA alleles are found to be associated with susceptibility and resistance to infectious diseases including HIV/AIDS, tuberculosis, and malaria that impose huge public health burdens in sub-Saharan Africa [22]. HLA studies have also yielded important insights into the role of pathogens in driving HLA polymorphism. For example, a study that analyzed 61 human populations across the world showed that populations that have a greater burden of pathogens show higher HLA diversity and those populations farther from Africa (geographic distance measured through land masses from Ethiopia) are characterized by lower HLA diversity [23].

Tuberculosis was a major selective force in the evolution of western European populations, whereas malaria served a similar role in Africa [24,25]. The subsequate introduction of TB in the malaria endemic by early Europeans may now account for the observed status of TB infections since these were TB naïve populations. Genes involved in protective immunity against diseases are always under greater selective pressure, showing greater variability than other genes [24,25]. For a disease to be a selective pressure in the evolution of a human population, the gene must have a significant impact for long periods of time, influencing morbidity and mortality before reproductive age [24,25]. Tuberculosis is currently a world-wide pathogen, and archeologic evidence indicates a great prehistoric prevalence for the disease in crowded cities of Europe and North Africa [26,27]. It appears, however, that this organism was once completely absent from several isolated areas [28,29], the largest of which was Africa [30]. Recent observations strongly suggest a significant role for genetic factors in innate resistance to infection by Mycobacterium tuberculosis [30]. This relation was discovered in a study of tuberculosis in Arkansas nursing homes and was supported by data from three outbreaks of tuberculosis in two prisons [30]. A person’s resistance level was found to correlate with the region of his or her ancestry [30]. Ancestors of persons’ in the more resistant group tended to derive from densely populated areas and cities rife with tuberculosis, whereas the ancestors of persons in the more susceptible group tended to derive from areas once free of tuberculosis [30] like the pre-colonial Africa (Table 1). With the completion of Human Genome Project and advances in genotyping technology, Genome-wide Association (GWA) Study has been one powerful tool for the study of genetic susceptibility in human complex diseases [31].

Gene Name Symbol Disease Type Result Population Reference
Arachidonate 5-lipoxygenase ALOX5 PTB + Ghana [32]
Butyrophilin-like 2 (MHC class II associated) BTNL2 PTB South Africa (Mixed) [33]
Cathepsin Z CTSZ PTB + The Gambia, Guinea-Bissau, Republic of Guinea, South Africa (Cape Town and Malawi) [34]
CD40 molecule, TNF receptor superfamily member 5 CD40 PTB The Gambia, Guinea-Bissau, Republic of Guinea [35]
CD209 molecule (DC-SIGN) CD209 PTB + The Gambia, Guinea-Bissau, Republic of Guinea, South Africa (Cape Town and Malawi) [36-38]
South Africa (Cape Town), Tunisia† [39, 40]
Chemokine (C-C motif) ligand 2 (Monocyte chemoattractant protein-1, MCP1) CCL2 PTB + − Ghana, Zambia South Africa(Cape Town) [41,42] [43]
Chemokine (C-C motif) ligand 3
Chromosome regions: 1p31 (15 Mb from IL12RB2), 21q22 (containing IFNGR2); 2p22-2p16, 8p12-8q11, 8q21-8q23, 9p21-9q12, 11q14-11q23, 19p13-19q12, 22p13-22q11 (no candidate genes)
Chromosome regions: 2p13-2q11 (containing the IL1 complex of genes), 3q23 (containing IL12A), 6p21 (containing MHC complex and TNF); 1p21-1q24, 8p12-8q11, 10q24-10q24, 11p15, 22p13-22q11 (no candidate genes)
Chromosome regions: 7p22-7p21 (containing IL6), 20q13 (containing MC3R and CTSZ)
Chromosome regions: 2q27 (17 Mb from SLC11A1); 2q14, 7q35-7q36, 8p22, 8p12-8q11, 14p13-14q11, 14q21-14q24 (no candidate genes)
Chromosome regions: 2q21-2q24, 5p13-5q22 (no candidate genes)
TNF levels PTB


Resistance to infection

Resistance to infection






South Africa (Malawi)









Chromosome region 8q12-q13 (gene not found) PTB (+) Morocco† [46]
Chromosome 15q microsatellite markers PTB (+) The Gambia, South Africa [47]
Chromosome Xq microsatellite markers PTB (+) The Gambia, South Africa [47]
Complement component (3b/4b) receptor 1 (Knops blood group) CR1 PTB + South Africa (Malawi) [44]
C-type lectin domain family 4, member M (LSIGN)
Cytotoxic T-lymphocyte-associated protein 4

South Africa (Cape Town)
Fucosyltransferase 2 FUT2 PTB The Gambia [49]
Group-specific component (vitamin D binding protein)
Intercellular adhesion molecule 1 (CD54)

South Africa (Xhosa, Cape Coloured) South Africa (Malawi) [50]
Interferon, gamma IFNG PTB, TB meningitis + The Gambia, Guinea-Bissau, Republic of Guinea, South Africa (Mixed) [51,52]
PTB South Africa (Malawi) [44]
Interferon gamma receptor 1 IFNGR1 PTB, TNF levels + The Gambia, Guinea-Bissau, Republic of Guinea, Uganda [51,53]
PTB The Gambia [54]
Interferon gamma receptor 2 IFNGR2 PTB The Gambia, Guinea-Bissau, Republic of Guinea [51]
Interleukin 1, alpha IL1A PTB + The Gambia [49]
Interleukin 1, beta IL1B PTB + The Gambia [55]
The Gambia [49]
Interleukin 1 receptor antagonist IL1RN PTB + The Gambia [49]
The Gambia [55]
Interleukin 8 IL8 PTB The Gambia [12]
Interleukin 10 IL10 PTB, IL10 levels, TNF levels + Ghana, South Africa (Malawi), Uganda [44,53,56]
PTB The Gambia, Ghana [49,56]
Interleukin 12 receptor, beta-1 IL12RB1 PTB + Morocco† [57]
Lymphotoxin alpha LTA PTB South Africa (Malawi) [44]
Major histocompatibility complex HLA PTB + South Africa (Venda) [58]
Mannose-binding lectin (protein C) 2, soluble (opsonic defect) MBL2 PTB The Gambia, South Africa (Malawi), Tanzania [44,59, 60]
Melanocortin 3 receptor Nitric oxide synthase 2, inducible MC3R NOS2 PTB
The Gambia, Guinea-Bissau, Republic of Guinea, South Africa (Cape Town and Malawi)
South Africa (Cape Town)
[34] [43]
Nucleotide-binding oligomerization domain containing 2 NOD2 PTB South Africa (Cape Town) [61]
Pentraxin-related gene
Protein tyrosine phosphathase, non-receptor type 22 (lymphoid)
Purinergic receptor P2X, ligand-gated ion channel, 7 P2RX7 PTB + The Gambia [63]
Solute carrier family 11, member 1 SLC11A1 Clinical TB, IL10 production, PTB, TB meningitis + The Gambia, Republic of Guinea, South Africa (Cape Town and Malawi), Tanzania [44,60,64,65,66,67]
PTB The Gambia, Morocco† [68,69]
Solute carrier family 11, member 2 SLC11A2 PTB, TB meningitis South Africa (Cape Town) [67]
SP110 nuclear body protein SP110 PTB + The Gambia, Guinea-Bissau, Republic of Guinea [70]
Ghana, South Africa [71, 72]
Surfactant, pulmonary-associated protein A1 SFTPA1 PTB + Ethiopia [73]
Surfactant, pulmonary-associated protein A2 SFTPA2 PTB + Ethiopia [73]
Toll-interleukin 1 receptor (TIR) domain containing adaptor protein TIRAP PTB, TB meningitis + Algeria† , The Gambia, Guinea-Bissau, Kenya, Republic of Guinea, South Africa (Mixed) [74,75]
PTB Ghana [76]
Toll-like receptor 2 TLR2 PTB, TNF levels + Tunisia† , Uganda [53,77]
PTB Guinea-Bissau, South Africa (Malawi) [37,44,53]
Toll-like receptor 4 TLR4 PTB, TNF levels + Uganda [53]
PTB, development of TB in HIV patients The Gambia, Guinea-Bissau, South Africa (Malawi), Tanzania [37,44,78,79]
Toll-like receptor 9 TLR9 PTB Guinea-Bissau [37]
Tumor necrosis factor TNF PTB South Africa (Malawi) [44]
Tumor necrosis factor receptor superfamily, member 1A TNFRSF1A PTB, TNF levels + Uganda [53]
Tumor necrosis factor receptor superfamily, member 1B TNFRSF1B PTB, TNF levels + Ghana, South Africa, Uganda [53,82]
Ubiquitin protein ligase E3A UBE3A PTB + The Gambia, Republic of Guinea, South Africa (KwaZulu-Natal) [80]
Vitamin D (1,25- dihydroxyvitamin D3) receptor VDR PTB + The Gambia, Guinea-Bissau, Republic of Guinea, South Africa (Venda) [18,19,37,58]
South Africa (Cape Town and Malawi), Tanzania [81,44,60]

Table 1: Genetic Associations with Tuberculosis in Africans


Infectious diseases remain an important component of human survival and continue to present a major threat for human populations world-over and consequently, shape their genetic diversity of. Tuberculosis remains very prevalent in sub-Saharan Africa despite the continued efforts to eradicate it through reforms in the environmental factors impelling its spread. In this antibiotic era, we continue to notice increase in the prevalence and incidences of TB especially in this region. The explanation to this intriguing conundrum may be masked in the host genetics


Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 11527
  • [From(publication date):
    October-2014 - Jun 28, 2017]
  • Breakdown by view type
  • HTML page views : 7778
  • PDF downloads :3749

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version