The Role of Smoking and Genetics


Limiting prenatal smoking may reduce MS risk, with genes and environment influencing brain development in children.

Multiple Sclerosis: The Role of Smoking and Genetics

Multiple Sclerosis (MS) is an autoimmune disorder diagnosed between the ages of 20 and 40. Limiting children’s exposure to prenatal smoking may lower the risk of developing MS.
Those with a family history or genetically predisposed to the disease are at greater risk of developing the disease. The research was published in the Journal of Neurology Neurosurgery & Psychiatry (1 Trusted Source
Environmental multiple sclerosis (MS) risk factors, genetic MS risk, and brain development in a general paediatric population

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Genes and Environment in Multiple Sclerosis Risk

The interplay of genes and environmental factors, including smoking, alter key aspects of brain structure in early childhood, likely facilitating the development of the disease and suggesting that there may be a window of opportunity to stave this off, conclude the researchers.

However, the cause of MS is still not clear whether it starts from early inflammatory brain damage or a latent neurodegenerative process overlaid with inflammation. Exactly when the disease process begins isn’t known either. But brain volume loss and poorer cognitive performance before clinical signs and symptoms appear suggest that these precede diagnosis.

Studies on migration show that early life environmental factors have a key role, but exactly how these interact isn’t yet known, they add. To shed more light on how and when the interplay of environmental and genetic risk factors might affect brain volume, and so facilitate future MS development, the researchers used data from the population-based Dutch Generation R study.

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Smoking’s Impact on Kids’ Brain Health

Participants in this study had good quality data on genotype and/or the known environmental risk factors of Epstein Barr virus infection, vitamin D levels, weight (BMI), parental tobacco exposure, and outdoor activity at the age of 5, plus high-quality brain scan images at the ages of 9 and 13.
In all, the researchers drew on imaging data showing brain volume for 5350 participants and brain microstructure for 5649 participants, none of whom had been diagnosed with MS.

Polygenic risk scores, derived from DNA samples, were used to assess the genetic risk of developing MS, with the genetic variant rs10191329, used as a marker of future MS severity. In all, 642 children tested positive for Epstein-Barr virus infection and 405 had been exposed to household parental smoking.

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Preventing MS by Reducing Smoke Exposure

The final analysis was based on genetic data from 2817 participants and brain volume and microstructure imaging data from 2970 participants. This showed an interplay between genetic and environmental risk factors for MS that was associated with certain aspects of brain structure during childhood and early teens.

Specifically, higher genetic risk for MS was associated with a strong immune response to Epstein-Barr virus infection, and it was also associated with increased susceptibility to the negative effects of household parental smoking on brain development. Higher MS genetic risk and household parental smoking interacted and were associated with lower total brain volume and grey matter volume, including thalamic volume.

No associations were observed for carriers of the rs10191229 genetic valiant. This is an observational study, and as such, no firm conclusions about cause and effect can be drawn.

Smoking, Genetics, and MS Risk in Children

By way of explanations for the findings, the researchers point out that higher Epstein-Barr virus antibodies may be caused by defective immune system control of this virus due to genetic risk for MS, possibly facilitating the development of the disease later in life.
The prevailing theory is that tobacco smoke produces chronic inflammation of the respiratory tract, thereby increasing the inflammatory activity of the immune system, they add.

“Our results importantly add another potential mechanism of tobacco smoke exposure in individuals with higher polygenic MS risk. The increased brain vulnerability to the effects of parental smoking may increase the exposure of [central nervous system] antigens to the developing immune system, increasing the risk of a brain-specific autoimmune disease,” they suggest.

“How this increased vulnerability influences other MS risk factors may open a window for prevention of MS by limiting childhood exposure to household smoking or other toxic exposures associated with MS (ie, household chemicals), and should be a focus for further studies,” they conclude.

Reference:

  1. Environmental multiple sclerosis (MS) risk factors, genetic MS risk, and brain development in a general paediatric population – (https://jnnp.bmj.com/content/early/2024/11/22/jnnp-2024-335053)

Source-Eurekalert



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