Lupus and its Relations to Ancestry

We all carry a part of people within us who came to life much before us. We are genetic continuity of our ancestors.  And we get some good and some unwanted genes from our ancestors. These unwanted genes make our body prone to certain diseases, we call them familial or genetic diseases. Family history increases the risk of many autoimmune or auto inflammatory diseases (1).

There are several situations in life when we want to know about the risk of getting or carrying the familial diseases. It could be due to the reason, that we may learn about the certain genetic disease in our parents, siblings, or some close relative. Lupus is dominantly the disease of women in the age of childbearing. Thus many women may also worry, and like to know about the risks of passing the genes to the coming generation.

There is no straightforward way of calculating this risk. But we know that certain kind of autoimmune diseases are familial, and they are conveyed by genes. There are lots of theories for calculating the hereditary risks, as medical science is still trying to sort out the mystery to the full extent. But what we know that most of these diseases, including lupus, are not passed by a single gene. Thus comes the theory of “cumulative hit hypothesis”, which states that if there are too many weak genes inside you, the certain kind of disease develops in the body. It is like having too many holes in the shield, and the risk of disease increases proportionally to the number of these holes or weak points. There is a strong accumulation of evidence in genetic studies that lupus is caused due to several such genes, and their accurate mapping may help predict lupus in future (2).

Other risk factors

But things are not that simple, genetics is not the sole risk factor. If someone has a close relative or a person is suffering from lupus, one may want to know the risk of the disease. This risk is difficult to calculate due to the interplay of many factors. In fact, even if two people have identical genes, it does not mean that both of them would develop the same diseases. This has been confirmed by the studies of identical twins (twins sharing the similar genetic code). Earlier it was thought that if one twin develops lupus, the risk for another twin is 69%, but now several newer studies have shown much lower risk. One study by Deafen et al. involving 107 twin pairs showed that the there was a concordance of only 24% in identical twins and just 2% in non identical twins (3).

This logically raises few questions. Whey some of the twins developed the disease and other does not. It is where the epigenetics comes into play(4). This shows the importance of environmental factors. Gene or collection of some weak genes are just a predisposing factor; they simply increase some one's chances of developing a poor disease. They indicate the poor defenses related to certain conditions. But finally, the environment has a lot to say. In the end, disease develops only if a person is exposed to certain environmental factors, also called “triggering factors” for autoimmune diseases.

The study of epigenetics says that environment can alter the gene expression(5). Meaning that a particular life style may increase or decrease the risk of developing familial diseases. This is exactly what is happening in the case of identical twins. Though both have the similar set of genes, but not both seem to develop the hereditary diseases. In fact, epigenetics go even further by stating that with a certain lifestyle, one can not only prevent the development of diseases but can also develop some genetical strengths that can be passed on to the next generation.

Though field like epigenetics is still in infancy, if we believe the adherents of this theory than a life style correction, controlling the flares in lupus would not only make your life better, but it can have a positive effect on the coming generations.

Reprogramming your genes

There is no way to change your ancestry, but having a knowledge about it can help you be better prepared and know more about the risk factors. Further, the evolution of fields like epigenetics can show us the ways of overcoming those genetic weaknesses. Epigenetics is not about changing the genes, but it is rather about influencing the behavior of the genes. By making changes in the lifestyle and environment we may be able to “reset” many of our health problem and diseases(6).

As we know that identical twins have the similar genetic makeup, but not similar disease pattern. Because the development of a disease like lupus is decided by the genes and their expression. Some environmental factors may force our genes to behave in an unexpected manner (change in genes expression), we can keep the weaker genes dormant by making changes in life and around.

To understand this concept better, just think of various organ tissues in our body, they all have the similar genetic code but still, they are so different in functionality and morphology. All this becomes possible because, in various cell and tissues, different subsets of genes are active and dormant. Thus the switching on or off of genes has the power to transform the behavior and structure of body cells. Toxins in an environment like pesticides, smoking, wrong dietary practices, sedentary life style, certain infections, stress conditions, all of them have the power to affect these switches on the genes.

Conclusion

Environment starts affecting us from the day we come into existence, that is much before we are even born. That is why there is the concept of so called intrauterine programming of our body composition (7), aging(8) or development of certain health conditions like diabetes and obesity(9).

In case of lupus, reprogramming can be done by early identification of lupus, knowing the exacerbating factors and avoid them (smoking, toxic pesticides, overexposure to the sun, avoiding smoking), treating the disease aggressively in early stage (10).

So to reprogram the genes, we may not need to change the basic code, but rather identify the factors that control or influence their expression. It seems that relationship between our behavior and genes is bi-directional. By avoiding the triggers that activate the bad genes, and strengthening the factors that suppress them, we may be able to reprogram the genes and even pass the benefits to the generations to come.

References

1. Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis, and treatment. CurrOpinRheumatol. 2005 Sep;17(5):586–99.

2. Langefeld CD, Ainsworth HC, Cunninghame Graham DS, Kelly JA, Comeau ME, Marion MC, et al. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017 17;8:16021.

3. Deafen D, Escalante A, Weinrib L, Horwitz D, Bachman B, Roy-Burman P, et al. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum. 1992 Mar 1;35(3):311–8.

4. Hewagama A, Richardson B. The genetics, and epigenetics of autoimmune diseases. J Autoimmun. 2009 Aug 1;33(1):3–11.

5. Weinhold B. Epigenetics: The Science of Change. Environ Health Perspect. 2006 Mar;114(3):A160–7.

6. Ho S-M, Johnson A, Tarapore P, Janakiram V, Zhang X, Leung Y-K. Environmental Epigenetics and Its Implication on Disease Risk and Health Outcomes. ILAR J. 2012 Dec 1;53(3–4):289–305.

7. Gale CR, Martyn CN, Kellingray S, Eastell R, Cooper C. Intrauterine Programming of Adult Body Composition. J ClinEndocrinolMetab. 2001 Jan 1;86(1):267–72.

8. Fernandez-Capetillo O. Intrauterine programming of ageing. EMBO Rep. 2010 Jan;11(1):32–6.

9. Tomar AS, Tallapragada DSP, Nongmaithem SS, Shrestha S, Yajnik CS, Chandak GR. Intrauterine Programming of Diabetes and Adiposity. CurrObes Rep. 2015 Dec 1;4(4):418–28.

10. Doria A, Arienti S, Rampudda M, Canova M, Tonon M, Sarzi-Puttini P. Preventive strategies in systemic lupus erythematosus. Autoimmun Rev. 2008 Jan 1;7(3):192–7.