Tensin 1 Gene Variants May Affect Nutrition in CF Patient Group
Cystic fibrosis (CF) patients with specific variants in the Tensin 1 gene may be at risk of low body mass index (BMI), a measure of nutritional status, if they carry the common CF-causing F508del mutation in both copies of the CFTR gene, a study reports.
This makes Tensin 1 (TNS1) a potential modifier gene in CF. A modifier gene is one that can influence disease severity by altering the effects of the underlying disease-causing mutation.
The study, “Tensin 1 (TNS1) is a modifier gene for low body mass index (BMI) in homozygous [F508del]CFTR patients,” was published in the journal Physiological Reports.
Mutations in the CFTR gene cause a thick mucus to build in patients’ lungs, pancreas, and other organs. Malnutrition and failure to thrive are among the earliest manifestations of CF due to mucus-blocked ducts in the pancreas, which is responsible for producing digestive enzymes.
Over 1,700 different CF-causing mutations have been identified in the CFTR gene to date, but the F508del mutation is the most common, being present in about 90% of all patients. If this mutation affects both copies of the CTFR gene, it is called homozygous; if only one, it’s heterozygous.
Prior research showed that CF severity is variable even among people with similar CFTR mutations, mostly due to the so-called modifier genes. This suggests that targeting modifier genes can be of benefit. To date, at least 56 modifier genes are known to affect CF disease severity.
Researchers at the Uniformed Services University of the Health Sciences, a part of U.S. government, led a study to identify additional CF modifier genes by performing a whole genome analysis.
They analyzed blood samples from 87 adults patients (mean age 35.9, 50% men) followed at the CF clinic at the University of California San Diego. The vast majority (92%) were of European ancestry. Forty-five were homozygous for the F508del mutation and the 42 others were compound heterozygous, meaning they had this mutation in one gene copy and a different mutation in the other copy. Most of these patients, 76.5%, had pancreatic insufficiency.
Whole genome sequencing revealed the presence of three single nucleotide polymorphisms (SNPs) in the TNS1 gene. Notably, TNS1, which codes for a protein implicated in the attachment of cells with their surrounding structure, had not previously been identified as a modifier gene for CF. (SNP refers to a difference in a single nucleotide, the building blocks of DNA.)
Among these three SNPs, two — rs918949T/T and rs2571445 — were linked with a lower BMI in patients homozygous for both F508del and one of these TNS1 variants, as compared with those homozygous for F508del but with a TNS1 variant in only gene copy.
“The Tensin 1 gene is thus a potential modifier gene for low BMI in CF patients homozygous for the [F508del] CFTR variant,” the scientists wrote. According to the team, this is the first modifier gene associated with BMI in CF.
No association was found between the SNPs and lung function, despite previous studies linking the TNS1 gene with lung health in chronic obstructive pulmonary disease patients.
Investigators noted this study’s small size as a limitation, as it may have masked the effects of TNS1 on the heterozygous patient group.