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Immune Response May be Linked to Ethnicity
#1
The ability of certain populations to evade infection is not a new concept in science. For example, people of West African descent, an area where malaria is highly prevelant, have some degree of protection against malaria. This is because the sickle cell allele alters the shape and function of the hemoglobin protein enough to prevent the malaria parasite from entering and infecting the host cell. People with one copy of the sickle cell allele have a natural degree of protection against malaria. People with two copies of the sickle cell allele, however, are affected with sickle cell anemia, a painful, debilitating condition in which the red blood cells are misshapen. The sickle cell allele remains within the population to provide protection against malaria.

Another example is the mutation of a co-receptor protein used by human immunodeficiency virus (HIV) that is found in European populations. HIV requires a main receptor on the cell, called CD4, to infect T cells. It also requires an additional co-receptor. Some strains of HIV utilize a co-receptor called CXCR4, and others utilize a co-receptor called CCR5. A mutation in the CCR5 gene, which is most commonly seen in European populations, prevents CCR5-tropic strains of HIV from entering the cell. This is because the virus is unable to properly bind to and recognize the cell. Individuals who have the CCR5 mutation are considered immune to these specific strains of HIV. In fact, an HIV patient who was treated with a bone marrow transplant from a donor with this CCR5 mutation was able to clear his HIV infection, and has not had detectable virus levels since the transplant.

These mutations likely occurred to help protect at-risk populations from infectious diseases. They are a functional way to prevent infection- they rely on changing the protein so that the infectious agent cannot gain entry to the cell. These mutations do not have an effect on the actual immune response developed in response to the infection. Rather, they help prevent the infection from being established in the first place.

The difference in a person’s ability to fight infection based on ethnicity has only recently been studied. Researchers from Simon Fraser University in British Columbia, Canada, sequenced the immunoglobulin heavy chain (IGH) gene in 425 volunteers of different ethnic origins. The IGH gene codes for a part of the protein that makes up most of the antibodies produced by humans. It is about 1 million nucleotides long, and consists of many segments that are rearranged in the B cell to produce unique antibodies. The researchers found astounding differences in the composition of the IGH gene based on ethnic origin in the volunteers after sequencing the genes. Some ethnicities seemed to have large deletions of segments of the IGH gene, as well as large insertions. The different composition of the IGH gene would result in a different array of antibodies being produced between the ethnic groups tested.

The researchers hypothesized that people are subjected to different types of pathogens in different parts of the world. Over time, portions of the IGH gene were either deleted or inserted in order to help the individuals produce antibodies needed against these pathogens. If one type of bacterium, for example, was not often seen in parts of Asia, the segments of the IGH gene that would develop antibody against that bacterium would eventually be lost from the gene. If this bacterium was a prominent threat to people in Europe, however, it would make sense that the IGH locus would maintain that portion of the gene in order to be able to produce the proper antibody.

The study results have implications for both treatments and vaccinations against infectious disease. Certain populations may not be able to respond with an effective immune response against a specific pathogen, meaning that alternative forms of treatment would be required to help remove the infection. In addition, if someone is unable to properly respond to a vaccination because he or she is unable to produce the desired antibody, the vaccine would be ineffective. This could prevent large areas of the world from benefiting from potentially life-saving vaccines. The research indicates that universal treatments and vaccines should be properly evaluated in diverse populations to ensure that everyone is able to benefit.



References:

http://www.upi.com/Science_News/2013/04/...366414892/
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#2
Ethnicity and lipoprotein diameter profile

Other associations of disease resistance with ethnicity have been recently highlighted in the literature, specifically related to insulin resistance and cardiovascular disease. A group in Birmingham, Alabama looked at mean lipoprotein particle diameters. Differences in the distribution of diameters of lipoproteins such as VLDL and HDL are associated with susceptibility to diseases including insulin resistance and cardiovascular disease. Lipoprotein sizes are associated with disease risk, but the profile of lipoproteins can be influenced by diet and exercise. Thus these present an attractive target for clinical interventions.

This study examined genetic differences which could impact on mean lipoprotein particle diameters between Caucasian, African-American, Chinese and Hispanic ethnic groups. They first assessed genotypes from Caucasian participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) and looked for association with fasting mean particle diameters. They then checked the Caucasian population of the Multi-Ethnic Study of Atherosclerosis (MESA) to determine if the associations observed were replicated before extending the analysis to the African-American, Chinese and Hispanic MESA populations.

The study found that two gene/lipoprotein density associations were notable. Firstly, variants in the apolipoprotein B (APOB) gene region, which encodes the primary apolipoproteins of chylomicrons and low-density lipoproteins (LDL), were significantly associated with mean VLDL diameter in the Caucasians both in GOLDN and MESA and with the Hispanic populations of MESA. Variation in the hepatic lipase (LIPC) gene, which encodes the enzyme that converts intermediate-density lipoprotein (IDL) to LDL, was associated with mean HDL diameter only in the Caucasians populations. Thus the findings seem to support ethnic variations in the genes directing at mean lipoprotein particle diameters, which have implications for ethnic-specific interventions in modification of lipoprotein profiles to target insulin resistance and cardiovascular disease.

Source
FRAZIER-WOOD, A. et al., 2013. Genetic variants associated with VLDL, LDL and HDL particle size differ with race/ethnicity. Human Genetics, 132(4), pp. 405-413
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Immune Response May be Linked to Ethnicity51