Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF
Abstract People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F5...
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| Format: | Article |
| Language: | English |
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Sociedade Brasileira de Genética
2024-03-01
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| Series: | Genetics and Molecular Biology |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572024000100104&tlng=en |
| _version_ | 1797216810280419328 |
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| author | Noémie Bélanger Anne Bonhoure Tamizan Kherani Valérie Boudreau François Tremblay Annick Lavoie Maite Carricart Ashish Marwaha Rémi Rabasa-Lhoret Kathryn J. Potter |
| author_facet | Noémie Bélanger Anne Bonhoure Tamizan Kherani Valérie Boudreau François Tremblay Annick Lavoie Maite Carricart Ashish Marwaha Rémi Rabasa-Lhoret Kathryn J. Potter |
| author_sort | Noémie Bélanger |
| collection | DOAJ |
| description | Abstract People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes. |
| first_indexed | 2024-04-24T11:51:52Z |
| format | Article |
| id | doaj.art-08515ed6cdce4296a264c67c8b40e92b |
| institution | Directory Open Access Journal |
| issn | 1678-4685 |
| language | English |
| last_indexed | 2024-04-24T11:51:52Z |
| publishDate | 2024-03-01 |
| publisher | Sociedade Brasileira de Genética |
| record_format | Article |
| series | Genetics and Molecular Biology |
| spelling | doaj.art-08515ed6cdce4296a264c67c8b40e92b2024-04-09T07:40:11ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852024-03-0147110.1590/1678-4685-gmb-2023-0021Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CFNoémie BélangerAnne BonhoureTamizan KheraniValérie BoudreauFrançois TremblayAnnick LavoieMaite CarricartAshish MarwahaRémi Rabasa-Lhorethttps://orcid.org/0000-0003-4706-5170Kathryn J. PotterAbstract People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572024000100104&tlng=enCFTR variantsCystic FibrosisOral Glucose Tolerance TestL206WA455E |
| spellingShingle | Noémie Bélanger Anne Bonhoure Tamizan Kherani Valérie Boudreau François Tremblay Annick Lavoie Maite Carricart Ashish Marwaha Rémi Rabasa-Lhoret Kathryn J. Potter Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF Genetics and Molecular Biology CFTR variants Cystic Fibrosis Oral Glucose Tolerance Test L206W A455E |
| title | Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF |
| title_full | Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF |
| title_fullStr | Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF |
| title_full_unstemmed | Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF |
| title_short | Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF |
| title_sort | association between cystic fibrosis transmembrane regulator genotype and clinical outcomes glucose homeostasis indices and cf related diabetes risk in adults with cf |
| topic | CFTR variants Cystic Fibrosis Oral Glucose Tolerance Test L206W A455E |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572024000100104&tlng=en |
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