Cystic fibrosis (CF) sufferers with particular variants within the Tensin 1 gene could also be prone to low physique mass index (BMI), a measure of dietary standing, in the event that they carry the frequent CF-causing F508del mutation in each copies of the CFTR gene, a research reviews.
This makes Tensin 1 (TNS1) a possible modifier gene in CF. A modifier gene is one that may affect illness severity by altering the consequences of the underlying disease-causing mutation.
The research, “Tensin 1 (TNS1) is a modifier gene for low body mass index (BMI) in homozygous [F508del]CFTR patients,” was revealed within the journal Physiological Reports.
Mutations within the CFTR gene trigger a thick mucus to construct in sufferers’ lungs, pancreas, and different organs. Malnutrition and failure to thrive are among the many earliest manifestations of CF as a result of mucus-blocked ducts within the pancreas, which is accountable for producing digestive enzymes.
Over 1,700 totally different CF-causing mutations have been recognized within the CFTR gene up to now, however the F508del mutation is the most typical, being current in about 90% of all sufferers. If this mutation impacts each copies of the CTFR gene, it’s referred to as homozygous; if just one, it’s heterozygous.
Prior analysis confirmed that CF severity is variable even amongst individuals with comparable CFTR mutations, principally because of the so-called modifier genes. This means that focusing on modifier genes will be of profit. To date, not less than 56 modifier genes are recognized to have an effect on CF illness severity.
Researchers on the Uniformed Services University of the Health Sciences, part of U.S. authorities, led a research to establish extra CF modifier genes by performing a complete genome evaluation.
They analyzed blood samples from 87 adults sufferers (imply age 35.9, 50% males) adopted on the CF clinic on the University of California San Diego. The overwhelming majority (92%) had been of European ancestry. Forty-five had been homozygous for the F508del mutation and the 42 others had been compound heterozygous, that means they’d this mutation in a single gene copy and a distinct mutation within the different copy. Most of those sufferers, 76.5%, had pancreatic insufficiency.
Whole genome sequencing revealed the presence of three single nucleotide polymorphisms (SNPs) within the TNS1 gene. Notably, TNS1, which codes for a protein implicated within the attachment of cells with their surrounding construction, had not beforehand been recognized as a modifier gene for CF. (SNP refers to a distinction in a single nucleotide, the constructing blocks of DNA.)
Among these three SNPs, two — rs918949T/T and rs2571445 — had been linked with a decrease BMI in sufferers homozygous for each F508del and one in all these TNS1 variants, as in contrast with these homozygous for F508del however with a TNS1 variant in solely gene copy.
“The Tensin 1 gene is thus a possible modifier gene for low BMI in CF sufferers homozygous for the [F508del] CFTR variant,” the scientists wrote. According to the crew, that is the primary modifier gene related to BMI in CF.
No affiliation was discovered between the SNPs and lung perform, regardless of earlier research linking the TNS1 gene with lung well being in chronic obstructive pulmonary disease sufferers.
Investigators famous this research’s small measurement as a limitation, as it might have masked the consequences of TNS1 on the heterozygous affected person group.