Is red hair gene linked to increased risk of Parkinson’s?


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"Redheads are more likely to develop Parkinson's," claims the Mail Online after a study found the gene that makes people with red hair susceptible to skin cancer also increases the risk of brain disease.


But the study didn't actually look directly at redheads (human ones, anyway). Instead, it used mice to look at whether a red hair gene called MC1R might be important in the region of the brain affected by Parkinson's. The study found the MC1R gene was active in this brain region in mice.


When researchers stopped the gene working, it led to nerve cells in this region dying, resulting in the mice developing progressive problems with movement.


The researchers suggested drugs targeting MC1R might help in treating Parkinson's.


The causes of Parkinson's disease in humans are not completely understood. While this research supports the possibility this gene plays a role, there are likely to be other genetic factors involved, as well as environmental factors.


Not all studies in humans have found a link between variants in the MC1R gene and Parkinson's. Even if there is some increase in risk associated with certain forms of this gene, it's likely to be relatively small.


Where did the story come from?


The study was carried out by researchers from Massachusetts General Hospital, Harvard Medical School and the University of California in the US, and the Tongji University School of Medicine in China.


The work was funded by the National Institute of Neurological Disorders and Stroke, the National Natural Science Foundation of China, the RJG Foundation, the Michael J Fox Foundation, the Milstein Medical Asian American Partnership Foundation, and the US Department of Defense.


The news headlines fail to capture the uncertainty about whether redheads are at greater risk of Parkinson's. Some studies have suggested this may be the case, but the evidence isn't conclusive.


The current research didn't look at this question directly – it looked at whether researchers could find a biological reason why there might be a link.


What kind of research was this?


This animal research looked at how a gene that determines whether people have red hair might also play a role in Parkinson's disease.


Other studies have suggested people with malignant melanoma – a skin cancer more common in redheads and fair-skinned people – might be at greater risk of Parkinson's. Studies have also shown higher than expected rates of melanoma in people with Parkinson's.


The researchers thought the link between the two conditions might be down to a gene called the melanocortin 1 receptor (MC1R) gene. People who carry certain versions of the MCR1 gene tend to have red hair and fair skin.


Some studies – but not all – have suggested carrying certain red hair MC1R variants and having red hair are also associated with an increased risk of Parkinson's disease.


The researchers wanted to look at whether the MC1R gene has an effect on nerve cells in the brain that produce a specific signalling chemical called dopamine.


In Parkinson's, these nerve cells die off, which causes the slow movement problems characteristic of the disease. If the gene is important in these cells, this would explain why there might be a link between red hair and Parkinson's.


Humans and other animals share many of their genes, so researchers often investigate what genes do in animals to give strong pointers of their roles in humans.


What did the research involve?


The researchers studied mice with a defective form of the MC1R gene. These mice have yellow coats, the equivalent of red hair in humans. The researchers compared these with normal mice with functioning MC1R genes.


They first looked at whether the MC1R gene in normal mice was active in the dopamine-producing nerve cells in the part of the brain affected by Parkinson's disease, the substantia nigra.


They compared the abnormal mice with the non-functioning MC1R gene and the normal mice to see whether the substantia nigra looked different and whether the mice moved differently. They also looked at how the defective gene might affect brain cells.


One way of producing mice with a Parkinson's-like condition is by exposing them to chemicals that kill the dopamine nerve cells.


The researchers looked at whether the abnormal mice were more susceptible to two different chemicals that can do this.


They then looked at whether "switching on" the protein made by the MC1R gene chemically might protect normal mice against the effects of one of these Parkinson's-inducing chemicals.


What were the basic results?


The researchers found the MC1R gene was normally active in the dopamine-producing nerve cells of the substantia nigra, which are typically affected by Parkinson's disease.


Mice with an inactive MC1R gene showed progressive problems with their movement. They moved around less in an open area compared with normal mice of a similar age, and the problem got worse as they aged.


These mice appeared to be losing dopamine-producing nerve cells in the substantia nigra.


Additional experiments suggested brain cells in these mice had more DNA damage from naturally occurring chemicals called free radicals.


The abnormal mice were more susceptible than normal mice to two different Parkinson's-inducing chemicals.


The researchers also found chemically activating the protein made by the MC1R gene in normal mice reduced the effects of these toxic chemicals.


How did the researchers interpret the results?


The researchers concluded that genetically "shutting off" MC1R signalling in mice leads to the death of some dopamine-producing nerve cells.


Conversely, "switching on" MC1R signalling helps protect these cells from damage by chemicals that normally produce Parkinson's-like effects in mice.


The researchers suggest this may mean drugs that target MC1R might help in Parkinson's. It also supports the possibility that the MC1R gene plays a role in the risk of both melanoma and Parkinson's disease.


Conclusion


This study looked at the role the red hair gene MC1R plays in the brains of mice. The findings suggest the gene has a part to play in keeping certain nerve cells in the brain alive.


The cells in question are those that die off in Parkinson's disease and cause the condition's characteristic movement problems.


These findings in mice are likely to need further investigation in human cells and tissue in lab studies.


Exactly what causes brain cells to die, causing Parkinson's disease, is unknown. As with many conditions, it's thought both genetic and environmental factors could play a role.


Research like this helps us gain a better understanding of the disease and how it might be treated or prevented.


But Parkinson's is a complex disease, and this new study has only looked at one small piece of a much bigger puzzle. For redheads, it may be comforting to know this link has not yet been proven beyond a doubt.


And not all studies in humans have found a link between variants in the MC1R gene and Parkinson's. In fact, a recent systematic review by some of the authors of this study looked into this.


The review gathered studies published to date that have investigated the link between red hair variants of the MC1R gene and Parkinson's disease.


Six studies assessing links with two variants of this gene were identified, but the studies couldn't quite exclude the possibility of no effect when pooled.


The review also identified two studies looking at hair colour. These studies found people with red hair were more likely to develop Parkinson's than people without red hair.


But these observational studies have several limitations – notably, they can't prove clear cause and effect because many other genetic, environmental and lifestyle factors could also be influencing any links seen.


And even if there is some increase in risk caused by this pigment gene, it's likely to be relatively small.


Links To The Headlines

Redheads are more likely to develop Parkinson's: Gene that makes gingers susceptible to skin cancer also drives up risk of brain disease, study reveals. Mail Online, March 3 2017


Ginger Gene: Ed Sheeran, Nicole Kidman and Prince Harry are at greater risk of these diseases – and their red hair is to blame. The Sun, March 3 2017


Links To Science

Xiqun Chen, Hongxiang Chen, Waijiao Cai, et al. The Melanoma-Linked "Redhead" MC1R Influences Dopaminergic Neuron Survival. Annals of Neurology. Published online January 23 2017



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by GetDoc Team

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