Increased Risk of IPF Found for Patients With Mucin 5B Genetic Variant

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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People carrying a genetic variant of the gene coding for Mucin 5B — a component of lung mucus and needed for cellular function — are at increased risk of developing idiopathic pulmonary fibrosis (IPF), according to a recent study.

In this variant, the nucleotide guanine, one of the building blocks of DNA, is switched to a thymine at one specific region in the gene.

This genetic variant leads to an increased risk of IPF across population subgroups, although the increase is most significant among Caucasians, the researchers found.

The study, “The minor T allele of the MUC5B promoter rs35705950 associated with susceptibility to idiopathic pulmonary fibrosis: a meta-analysis,” was published in the journal Scientific Reports.

IPF is a respiratory system disease characterized by fibrosis (scarring) of the lungs with no clear cause — though the role of genetic factors in the diagnosis and progression of this condition has received more attention in recent years.

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Analysis of Lung Tissue Reveals Important Genetic Drivers of IPF

Research has shown that as many as 20% of IPF patients have reported family members with pulmonary fibrosis, which may indicate a hereditary or genetic component.

Mucin 5B (MUC5B) plays a role in immune regulation by maintaining cellular function within the airways and alveoli — the tiny air sacs in the lungs where gas exchange occurs — through its role in maintaining the lung’s mucus.

Previous studies have found that a single nucleotide polymorphism (SNP) — a common variation at a single point in a gene — in the promoter region of the MUC5B gene shows a strong association with IPF risk and is present in 30–35% of IPF patients. The promoter is the region within a gene that is responsible for controlling its activity. It is in this region that the nucleotide guanine (G) is switched to a thymine (T).

Now, researchers performed a meta-analysis, examining data from a large number of completed studies, to determine the correlation between this particular SNP genetic variant, called rs35705950, and IPF risk.

A total of 24 studies were selected to be included in the analysis. Altogether, they included a total of 6,749 IPF patients and 13,898 healthy people, who served as controls. Among the participants were 5,100 Caucasian, 1,090 Asian, and 559 mixed population patients.

Using a heterogeneity test, which looks at the variation in outcomes between studies, researchers showed that the T-allele, unlike the G-allele, was associated with IPF risk. Of note, an allele is an alternative form of a gene.

Additionally, they found that when comparing the T and G alleles in various populations, including Caucasian, Asian, and mixed population groups, the T-allele was still associated with IPF risk.

The team then used another analysis model to evaluate the correlation between MUC5B possible allele combinations and IPF susceptibility.

By analyzing genotypes — the individuals’ genetic makeup — they found that people carrying two T-alleles (TT genotype) had a 10 times higher risk of developing IPF than those carrying two G-alleles (GG genotype).

This increased IPF risk associated with the TT genotype was seen across all patient populations. It was highest in mixed population patients, with a 32.83 times higher risk, followed by Caucasians, with a 10.98-fold higher risk, and Asian patients, where the risk was increased 4.29 times.

Individuals carrying one T- and one G-allele (GT genotype) had a 4.84 times higher risk of developing IPF compared with those with the GG genotype. As was previously found, compared with the GG genotype, the GT genotype was associated with an increased IPF risk across different populations, with the risk being higher among Caucasian patients (6.27 times higher).

After combining individuals with the GT and TT genotypes, and comparing them with those with the GG genotype, researchers arrived at the same conclusion: patients harboring at least one T-allele were 4.84 times more likely to develop IPF. This increased risk was also seen across all populations, particularly among Caucasian patients (6.30 times higher).

Investigators then performed a final comparison, in which they compared IPF risk among individuals with the TT genotype with those harboring the GG or GT genotype. This analysis indicated that those with the TT genotype had a 5.11 times increased risk of IPF compared with those carrying at least one G-allele.

The TT genotype also was associated with an increased risk of IPF across all populations compared with the GG and GT genotype, especially among mixed populations patients (22.94 times higher).

“The meta-analysis results showed that people with T minor allele in Caucasian, Asian and mixed populations were more likely to be susceptible to pulmonary fibrosis, and those with TT genotype were more likely to be susceptible to IPF than those with GT genotype,” the researchers wrote.

They also noted “the association strength of minor T allele in Caucasian population was more significant than that in Asian population.”

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