Shorter telomeres, protective caps for DNA, may raise IPF risk

Obesity and tobacco smoking also thought to affect telomere length

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by Andrea Lobo |

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People with shorter telomeres, or chromosome “caps,” may be at a greater risk of developing idiopathic pulmonary fibrosis (IPF), a study reported.

This work “also provided some interesting genetic evidence to prove that obesity and exposure to tobacco smoking as a fetus might also contribute to the development of the fibrotic [disease],” the researchers wrote. Previous studies suggest a link between obesity and/or smoking and shorter telomeres, they added, noting the associations found here should be confirmed in future studies.

The study, “Genetic association of telomere length, obesity and tobacco smoking with idiopathic pulmonary fibrosis risk,” was published in the journal BMC Public Health.

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Telomeres help to protect DNA in cells from damage

IPF, a form of pulmonary fibrosis (PF) that lacks a clear underlying cause, is characterized by progressive lung tissue scarring, or fibrosis, leading to shortness of breath and other disease symptoms. It also tends to occur in middle-age and older adults, and telomeres length can be affected by the aging process.

Telomeres are structures that cap the ends of chromosomes, helping to protect DNA from damage. Abnormally short telomeres have been tied to an higher risk of a variety of conditions, including PF.

“An increasing number of observational studies focused on the potential effects of … telomere-associated factors (i.e. tobacco smoking, alcohol drinking, and obesity) on the risk of IPF, and provided some interesting findings,” the researchers wrote.

Scientists at institutes in Zhengzhou, China, aimed to validate these reported observations by using genome-wide association studies to explore the genetic effects of telomere length and telomere-associated factors on IPF risk. Genome-wide association studies are those that scan all genes, or the genome, looking for small genetic alterations, called single nucleotide polymorphisms (SNPs), that are found more often in people with a particular disease.

Data collected came from a U.K. biobank with 472,174 participants, with a focus on genetic variants potentially associated with telomere length and the linking of telomere length to certain conditions. IPF data were obtained from a database including 1,812 people in Europe with the disease and 338,784 without it as controls.

Longer telomere length was found to associate with a reduced risk of IPF, with risk being 52.5% lower for each standard deviation increase in telomere length. This risk was calculated after excluding SNPs linked to obesity and smoking. (Standard deviation or SD is a statistical measure of how much variation there is within a dataset, or how close or far apart data points spread from the mean.)

Obesity and smoking, linked to telomere length, seen as possible IPF causes

Next, they analyzed factors associated with telomere length, including obesity, tobacco smoking, and alcohol drinking. Obesity was determined by a person’s body mass index (BMI) and body fat percentage (BFP), both measures of body fat.

Higher BMI and BFP values linked with an increased risk of developing IPF. That risk was 42.5% times higher per each SD increase in BMI, and 70.2% per each SD increase in BFP.

People whose mothers smoked during pregnancy also were at a higher risk of IPF — a risk found to be 13.18 times higher per SD increase in the prevalence of maternal smoking.

“These results were consistent with one important medical truism that many organs of the fetus (including the lungs) were at a developmental stage and were susceptible to damage from tobacco,” the researchers wrote, and findings warrant further investigation.

No associations were seen between heavy smoking, smoking initiation, age of smoking initiation, smoking cessation, and the risk of developing IPF. Similarly, heavy drinking did not associate with a higher risk of the disease.

“In conclusion, the present study confirmed the causal association of [telomere length] with the risk of IPF,” the researchers wrote. It also demonstrated that factors that might influence the length of telomeres, such as “obesity and exposure to tobacco smoking as a fetus might also contribute to the development of [IPF].”

When exploring the effect of telomere length on one disease, it is important to consider that telomere length decreases progressively with age, so study groups should be of similar ages. A significant age difference between data sets in this study, and that was noted as an important limitation by its authors.

Therefore, “these findings should be verified by future studies,” the researchers noted.

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