A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Rare gene variants and weight loss at 10 years after sleeve gastrectomy and gastric bypass - a randomized clinical trial




TekijätLoid, Petra; Grönroos, Sofia; Hurme, Saija; Salminen, Paulina; Mäkitie, Outi

KustantajaElsevier

Julkaisuvuosi2024

JournalSurgery for Obesity and Related Diseases

Tietokannassa oleva lehden nimiSurgery for Obesity and Related Diseases

ISSN1550-7289

eISSN1878-7533

DOIhttps://doi.org/10.1016/j.soard.2024.11.021

Verkko-osoitehttps://doi.org/10.1016/j.soard.2024.11.021

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/484735822


Tiivistelmä

Background
Genetic background of severe obesity is inadequately understood. The effect of genetic factors on weight loss after metabolic bariatric surgery (MBS) has shown inconclusive results.ObjectivesTo determine the prevalence of rare obesity-associated gene variants in a secondary analysis of a randomized clinical trial (RCT) comparing laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) for the treatment of severe obesity and examine their association with long-term weight loss at 10 years.SettingUniversity Hospital, Finland.MethodsTargeted sequencing panel was used to examine variants in 79 obesity-associated genes and 16p11.2 copy number variants. Weight loss was evaluated by percentage total weight loss (%TWL).
Results
Out of 240 patients, 113 patients [mean body mass index 48.4 kg/m2, (6.8 standard deviation [SD]) kg/m2 and median age 49 (range 26–64) years, LSG n = 60, LRYGB n = 53] were available for this post-hoc study. We identified 7 rare heterozygous likely/suspected pathogenic (LP/SP) variants in SH2B1, PCSK1, DNMT3A, BDNF, and AFF4 in 6 patients (5.3%), 5 heterozygous variants of uncertain significance in PLXNA4, PLXNA2, NRP1, and SEMA3D in 5 patients (4.4%), heterozygous Bardet-Biedl syndrome variants in 3 patients (2.7%), and PCKS1 risk allele p.Asn221Asp in 9 patients (8.0%). The patients with LP/SP variants had earlier age of obesity onset (P = .0089) and higher %TWL (P = .0446) compared with patients without LP/SP variants.ConclusionsThere were LP/SP pathogenic variants in 5% of the patients supporting the potential benefits of genetic testing to optimize targeted therapies in the future. Despite deleterious gene defects the long-term MBS outcome can be favorable.

Ladattava julkaisu

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Julkaisussa olevat rahoitustiedot
This study was supported by Sigrid Juselius Foundation, the Foundation for Pediatric Research, the Academy of Finland, Folkhälsan Research Foundation, Finska Läkaresällskapet, and Stiftelsen Dorothea Olivia,
Karl Walter och Jarl Walter Perklens Minne.


Last updated on 2025-18-02 at 11:01