Genetic changes explain why some of us are more sensitive to gluten than others and how it leads to celiac disease
From Weight Watchers to Atkins to Juice Cleanses, we live in a society that continuously swings through diet fads. When you walk into any supermarket, it is hard to miss the latest food trend embraced by consumers and the food industry alike; the gluten-free diet. Gluten is a protein normally found in grains like wheat, rye or barley, and gives bread the chewy texture that we all love. However, when the gluten in your diet signals your immune system to target normal, healthy cells, it leads to celiac disease (CD). The best predictor of CD is genetic variation, as there are versions of genes involved in the immune system that can predispose you to CD.
What is Celiac Disease?
Celiac disease is an autoimmune disease – it is caused by your immune system attacking and destroying healthy cells. CD differs from food allergies, because antibodies, which are involved in an allergic reaction, do not play a role in the autoimmune response occurring in CD. Also, CD symptoms usually take 48-72 hours to develop, compared to the immediate reaction seen with food allergies. Initial signs of CD include digestive problems like bloating, stomach aches and diarrhea. These symptoms can often be mistaken for a number of other conditions, like lactose intolerance or Crohn’s disease, and, if left undiagnosed, the symptoms of CD will worsen and can be fatal. The main risk factors for CD are genetic changes in two immune system genes, HLA-DQA1and HLA-DQB1.
HLA genes encode proteins that are normally involved in alerting the immune system against foreign bodies, such as viruses and bacteria. When a person with CD eats anything that contains gluten, the mutated HLA proteins recognize gluten as foreign. This detection of a foreign component signals special immune cells, called T-cells, to mount an immune response. The inflammation from the aberrant immune response leads to severe damage to the intestinal lining and the loss of cells that are essential for the absorption of nutrients. Serious damage to the intestinal lining can lead to more severe symptoms like anemia, osteoporosis, infertility, depression and epilepsy.
Genetic changes in HLA-DQA1 and HLA-DQB1 predispose individuals to CD; but only a subset of the people with these genetic changes, will actually experience gluten-intolerance. This indicates that other genetic and environmental factors are also involved in the development of CD. Moreover, individuals with non-classical CD develop secondary health problems, like anemia and chronic fatigue, without having any of the typical digestive symptoms, making it difficult to diagnose CD solely based on symptoms.
The Gluten-Free Fad
The gluten-free movement was spurred on by a study lead by an Australian group in 2011, stating that gluten causes digestive problems, even in people without celiac disease. Yet two years later, the same group failed to duplicate these results. However, the damage was already done; in Australia for every person diagnosed with CD, 20 additional people were following a gluten-free diet. In the US, retail sales from gluten-free products are predicted to reach 23.9 billion US dollars by 2020 – a massive 6-fold increase from the 3.8 billion dollars in 2011.
While eliminating gluten from your diet has no obvious drawbacks, undiagnosed celiac disease can be dangerous, because even small amounts of gluten can cause severe intestinal damage, leading to life threatening conditions. If you think you might be sensitive to gluten, a proper diagnosis of celiac disease, especially if it runs in your family, just might save your life.
Do You Carry the Genes for Celiac Disease?
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The use of pharmacogenomics may be of reach to everyday consumers in the near future. In one of the first projects of its kind in North America, 33 community pharmacies in British Columbia, Canada, will be working with 200 volunteer patients to provide them with personalized medication.
The program named “Genomics for Precision Drug Therapy in the Community Pharmacy” was funded by the BC Pharmacy Association (BCPhA) and Genome British Columbia (Genome BC). Research and analysis for the project is currently being performed at the University of British Columbia’s Faculty of Pharmaceutical Sciences.
During the course of the project, the volunteers had their saliva samples collected by pharmacists at participating locations. These samples were then sent to researchers at the university for DNA sequencing. Researchers at this stage of the program are currently analyzing all the samples in order to better understand how proper drug dosages can be determined through looking into the volunteers’ genetic makeup. Once the analysis is complete, they will send the results back to the pharmacies where samples were initially collected. The pharmacists can then use the data to be able to know the proper drugs needed to give their patients as well as the proper dosage amounts.
Pharmacogenomics has in recent years been used in finding proper drug dosages and treatments for cancers and rare diseases. However, it has not been used for other kinds of medication such as for treating mental health. Personalized treatment can be beneficial for all patients, but finding a way to reach-out to all of them for sequencing can be tricky.
This project could potentially tackle this problem through the use of pharmacies as a gateway to reach local communities. Having access to personalized medicine can provide many advantages. By allowing pharmacies to offer this to everyday patients, one of the greatest benefits will be the opportunity to greatly diminish the chances of adverse drug effects.
A massive study looking into the influences that genetics may have in cancer has recently been published in the Journal of the American Medical Association. The researchers monitored over 200,000 twins in order to generate estimates of the risk of heritability in 23 different types of cancers.
Nordic Twins from Denmark, Finland, Norway, and Sweden were followed for an average period of 32 years between 1943 and 2010. A total of 27,156 diagnoses of cancers were found in 23,980 of those individuals, which provided the statistic of 32% cumulative incidences.
It is known that identical twins share the same genetics, while fraternal twins share half of the same DNA. Provided that certain cancers did have hereditary components, the risk of a second twin developing cancer would therefore be greater in identical twins.
The method in which researchers estimated familial risk and heritability was through time-to-event analyses as well as with follow-ups through cancer registries.
It was found that when one twin had developed cancer, the other twin in turn had a greater risk in being diagnosed with cancer. In identical twins, an absolute 14% risk was found while in fraternal twins, an absolute 5% was found. Through all the statistics generated from monitoring 23 different types of cancers in thousands of twins through the years, they concluded that the heritability of cancer was overall 33%. This was shown to be in particular with skin melanoma, prostate cancer, non-melanoma skin cancer, ovarian cancer, breast cancer, kidney cancer, and uterine cancer. They all had a risk above average of developing in the second twin.
An interesting find in the study was when both twins had developed cancer, 2/3 of those siblings were diagnosed with different kinds of cancers. The team of researchers believes that these results imply that in some families, there is a common increased risk for cancer.
According to the published report, the researchers further concluded, “this information about hereditary risks of cancers may be helpful in patient education and cancer risk counselling.”
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About DNA Paternity Testing
Resemblances between a parent and child can sometimes be hard to see. When families wish to discover the true biological relationship between an alleged father and child, the most reliable method is through genetic testing. Undergoing a paternity test provides definitive genetic proof of whether a male is the true biological father of a child. By simply brushing the inside cheeks of each individual with a buccal swab, samples can be tested and compared in order to determine conclusively whether an alleged father is in fact the true biological father.
Humans are composed of trillions of cells. Those cells contain all of our genetic information in the form of DNA. Hence why when a seemingly small swab sample is sent to the lab for testing, scientists are able to create a DNA profile for that individual. DNA – like a fingerprint – is what makes us all unique. As a child obtains half of their genetic information from their biological mother, and the other half from their biological father, the “genetic blueprint” of an alleged father can be analyzed and compared to the genetic profile of a child to determine paternity.
But how exactly is such an amount of genetic information condensed and tested?
Specific sections of the individual’s DNA are amplified by a process known as polymerase chain reaction (PCR). When amplified, these particular sections of DNA create a type of pattern for an individual. By viewing and comparing the pattern of an alleged father with that of a child, the picture becomes clear as to whether the individual is the true biological father. Should the child have half of his or her DNA pattern match that of the alleged father, there is a genetic match. If the patterns however do not overlap, then the individual is not the biological father.
Aside from being able to visually see the frequency of the patterns, the results of a DNA paternity test are given in numeric form, and calculated to determine the probability of paternity. Lab results for paternity testing are guaranteed to be 100% accurate for paternity exclusions (not the father of the child), and over 99.9% for paternity inclusions.
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