CHAPTER 10 TABLES
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Genetics and Public Health in the 21st Century
Table 1. Malaria, TB, and HIV/AIDS: transmission, prevention and risk groups
| Disease | Pathogen (type) | Transmission | Prevention | At-risk population |
|---|---|---|---|---|
| Malaria | Plasmodium spp. (parasite) | Vector (Anopheline mosquito), blood | Prevent vector contact, chemoprophylaxis | Children and pregnant women in endemic areas. All age groups in nonendemic areas |
| Tuberculosis (TB) | Mycobacterium tuberculosis (acid-fast bacillus) | Aerosol | Reduce exposure, BCG vaccine, chemoprophylaxis | Children, adults, immunocompromised persons |
| HIV/AIDS | Human immuno- deficiency virus type 1 (HIV-1)(lentivirus) | Sexual contact, blood or blood products | Reduce exposure, chemoprophylaxis | Fetus/neonate (vertical transmission), adolescents, adults |
Table 2. Host genes, impact on infectious diseases, and population frequency
| Disease | Gene/ genotype | Chromo-some location | Impact of gene/genotype on infectious diseases | Population frequency | *References | ||
|---|---|---|---|---|---|---|---|
| Resis-tance | Susceptibility | Disease outcome | |||||
|
Malaria
|
Duffy antigen negative
|
1p22.1 and 1q12-q21
|
+
|
Total protection against P.vivax infection
|
Africans near 100%
Absent in Caucasians and Mongolians
|
27, 28
|
|
|
Sickle-cell trait
(Hb AS)
|
11
|
+
|
|
> 90% protection against falciparum cerebral
malaria, severe anemia and death
|
Kinshasa, Zaire 26%
Ibadan, Nigeria 24% Accra, Ghana 8% Kampala, Uganda 19% Kisumu, Kenya 25%
|
31-34
|
|
|
α-thalassaemia
|
16pter-p13.3
|
+
|
|
Reduction of risk of severe malaria to 0.40
in homozygotes, and to 0.66 in heterozygotes Reduction in risk of hospital admissions due to other infections 0.36 in homozygotes, and 0.63 in heterozygotes
|
Tharu, Nepal 80%
Vanuatu 8-38% Papua New Guinea 4-38% |
36, 37 38, 39 |
|
|
β-thalassaemia
|
11p15
|
+
|
|
Partial protection against severe disease
in Liberia (P.Falciparum)
|
Variable frequencies |
40
|
|
|
Melanesian
ovalocytosis |
17q21-q22
|
+
|
|
Band 3 deletion not found in patients with
cerebral malaria in Papua New Guinea. Protection against severe disease |
Up to 30% in aboriginal
population in south-east Asia and Pacific islands Absent in Africans |
41, 42
|
|
|
G6PD deficiency
|
Xq28
|
+
|
|
46-58% reduction in severe malaria for both
male hemizygotes and female heterozygotes in the Gambia
|
Female heterozygotes
in Gambia 13.7% in Kenya 27.3% Male hemizygotes in Gambia 5.9% in Kenya 18.8%
|
43
|
|
|
HLA-B53
|
6p21.3
|
+
|
|
Partial protection (4-50%) against cerebral
malaria and anemia |
Nigerians 40%
Gambians 25% Zambians 21% Zimbabweans 16% South Africans 2% Caucasians and Orientals 0-1% |
35
|
|
|
DRB1*1302
|
6p21.3
|
+
|
|
Protection against severe malaria anemia
|
Northern Italian
2.97% |
**
|
|
|
TNF-2 homo-zygote
[a poly-morphism in the promoter region of TNF-a gene (-308)] |
6p21.3-
q21.1 |
|
+
|
7- fold increased risk of death and neuro-
logic sequealae due to cerebral malaria |
Gambians,
TNF-2 allele frequency 0.16 |
45
|
|
|
ICAM-1
|
19p13.3-
p13.2 |
|
+
|
2-fold increased susceptibility to
cerebral malaria |
Kenya >30%
Caucasians rare or absent |
46
|
|
* The references are for the population frequencies. The references for the disease outcome are already included in the text
** HLA 1998 Gjertson DW and Terasaki PL ed, American Society for Histocompatibility and Immunogenetics (ASHI)
Table 2 (cont’). Host genes, impact on infectious diseases, and population frequency
| Disease | Gene/ genotype | Chromo-some location | Impact of gene/genotype on infectious diseases | Population frequency | *References | ||
|---|---|---|---|---|---|---|---|
| Resistance | Susceptibility | Disease outcome | |||||
|
TB
|
Tay-Sachs(TS)
gene |
15q23-q24
|
?
|
|
No evidence of protection against TB
|
TS carriers ~ 4%
|
60, 61
|
|
HLA-DR2
|
6p21.3
|
|
+
|
DR2 associated with TB severity
|
DRB1*1501/ DRB1*1502 |
***
|
|
|
†DRB1 *1501
|
|
+
|
DRB1*1501 and DRB1*1502 both
associated with severity and radiogra- phic extent of clinical TB |
||||
|
†DRB1*1502
|
|
+
|
DRB1*1501 and DRB1*1502 both
associated with drug failure in TB treatment |
||||
|
HLA-DQB1 *0503
|
6
|
|
+
|
Associated with clinical TB
|
Cambodians <1%
Caucasian US 1.7%
|
50 ** |
|
|
NRAMP-1
|
2q35
|
|
+
|
4-fold increased risk of TB in
persons heterozygous for INTR4 and 3’UTR polymorphisms |
Allelic frequency in
Gambians 3%
|
17
|
|
|
IFN-γ R
|
6q23-q24
|
|
+
|
Both associated with non-TB
mycobacterial disease. |
no published data
|
78, 79
|
|
|
IL12R (IL12B1)
|
19p13.1
|
|
+
|
Only IFN-γ R is associated with
adverse events post BCG vaccination |
|||
|
Vitamin D
receptor (VDR) |
12q12-q14
|
|
+
|
tt homozygosity associated with
increased risk of TB disease |
t allele frequency
in Caucasian 45% |
****
|
|
†DRB1*1501 and 1502 are HLA-DR genotypes that type serologically as HLA-DR2
*** Proceedings of the 11th International Histocompatibility Workshop and Conference. Yokohama, Japan 1991
**** Hill AVS, Ruwende C, Corrah T et al. Association of immunognetic variants with susceptibility to tuberculosis in West Africa.
Q J Med. 1996; 89: 868
Table 2 (cont’). Host genes, impact on infectious diseases, and population frequency
| Disease | Gene/ genotype | Chromo-some location | Impact of gene/genotype on infectious diseases | Population frequency | *References | ||
|---|---|---|---|---|---|---|---|
| Resis-tance | Susceptibility | Disease outcome | |||||
|
HIV
|
HLA class I/II
|
6p21.3
|
+
|
+
|
Faster progression associated with
alleles B7, B27, DR7, haplotype A1-B8-DR3, and homozygosity status Reduction of vertical transmission with class I disparity |
Caucasians
10% B7, 4% B27, 13% DR7 3% haplotype A1-B8-DR3 |
90
|
|
TAP (often
in combination with HLA) |
6p21
|
|
+
|
Influence on progression
|
no data on
frequency |
90
|
|
|
Δ 32 CCR5
|
3p21
|
+
|
|
Homozygosity associated with resistance Heterozygosity associated with delayed |
Homozygosity
Caucasians <1% Heterozygosity Caucasians10-20% African Americans 6% Hispanics 7% Native Americans 13%
|
20
|
|
|
CCR2-V64I
|
3p21
|
+
|
|
Delayed-progression to AIDS
|
Caucasians 10%
Asians 25% |
20, 80
|
|
|
SDF1-3’A
|
10q11.1
|
?
|
|
Influence on progression
|
Caucasians 21%
Hispanics 16% African Americans 6% Asians 26% |
95
|
|
|
TNF-α
|
6p21.3
|
|
?
|
Long-term non progression
|
no data on frequency
|
99
|
|
Table 3. From Host Genes to Public Health Actions: Prevention and Control of Infectious Diseases
| Prevention Strategy for Infectious Diseases | Incorporation of Host Genetic Information |
|---|---|
| Surveillance and Response ——–> | Existing Surveillance Systems Data collection by HuGE Net Population based surveys of the prevalence of genetics factors Surveillance systems of infectious diseases in Local and State Departments of Health and by Federal Government Agencies |
| Applied Research ———————> | Genetic Studies, Genetic Engineering Association and linkage studies, assessment of the interactions between genetics and environmental factors Clinical trials, assessment of the efficacy of or adverse outcomes to vaccines, antibiotics, gene therapy or other interventions Assessment of new technology Behavioral sciences and program evaluation |
| Infrastructure and Training———> | Partnership and Information Dissemination Funding, laboratory support, training of public health professionals, global surveillance network development Information exchange, education of the lay public, and advocacy groups |
| Prevention and Control————–> | Reinforcement of Classical Measures Primary, secondary, and tertiary prevention |
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