The Journal of clinical endocrinology and metabolism · 2017
Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention.
СтатьяМногоцентровое исследованиеРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Billings Liana K, Jablonski Kathleen A, Warner A Sofia, Cheng Yu-Chien, McAteer Jarred B, Tipton Laura, Shuldiner Alan R, Ehrmann David A, Manning Alisa K, Dabelea Dana, Franks Paul W, Kahn Steven E, Pollin Toni I, Knowler William C, Altshuler David, Florez Jose C, Diabetes Prevention Program Research Group
Аннотация
CONTEXT: Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits.
OBJECTIVES: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions.
DESIGN AND SETTING: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP.
PARTICIPANTS AND INTERVENTIONS: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944).
MAIN OUTCOME MEASURES: Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism × treatment interaction (Pint < 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits.
RESULTS: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups.
CONCLUSIONS: These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.
OBJECTIVES: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions.
DESIGN AND SETTING: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP.
PARTICIPANTS AND INTERVENTIONS: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944).
MAIN OUTCOME MEASURES: Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism × treatment interaction (Pint < 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits.
RESULTS: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups.
CONCLUSIONS: These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.
Предметные рубрики MeSH
Basic Helix-Loop-Helix ProteinsDiabetes Mellitus, Type 2Exercise TherapyGenetic VariationGlucokinaseHepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 4Homeodomain ProteinsHumansMetforminMutation, MissensePolymorphism, Single NucleotideRisk Reduction BehaviorTrans-ActivatorsTreatment OutcomeWeight Reduction Programs