BibTex format
@article{Mercader:2017:10.2337/db17-0187,
author = {Mercader, JM and Liao, RG and Bell, AD and Dymek, Z and Estrada, K and Tukiainen, T and Huerta-Chagoya, A and Moreno-Macias, H and Jablonski, KA and Hanson, RL and Walford, GA and Moran, I and Chen, L and Agarwala, V and Luisa, Ordonez-Sanchez M and Rodriguez-Guillen, R and Rodriguez-Torres, M and Segura-Kato, Y and Garcia-Ortiz, H and Centeno-Cruz, F and Barajas-Olmos, F and Caulkins, L and Puppala, S and Fontanillas, P and Williams, AL and Bonas-Guarch, S and Hartl, C and Ripke, S and Tooley, K and Lane, J and Zerrweck, C and Martinez-Hernandez, A and Cordova, EJ and Mendoza-Caamal, E and Contreras-Cubas, C and Gonzalez-Villalpando, ME and Cruz-Bautista, I and Munoz-Hernandez, L and Gomez-Velasco, D and Alvirde, U and Henderson, BE and Wilkens, LR and Le, Marchand L and Arellano-Campos, O and Riba, L and Harden, M and Gabriel, S and Abboud, HE and Cortes, ML and Revilla-Monsalve, C and Islas-Andrade, S and Soberon, X and Curran, JE and Jenkinson, CP and DeFronzo, RA and Lehman, DM an},
doi = {10.2337/db17-0187},
journal = {Diabetes},
pages = {2903--2914},
title = {A loss-of-function splice acceptor variant in IGF2 is protective for type 2 diabetes},
url = {http://dx.doi.org/10.2337/db17-0187},
volume = {66},
year = {2017}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Type 2 diabetes (T2D) affects more than 415 million people worldwide, and its costs to the health care system continue to rise. To identify common or rare genetic variation with potential therapeutic implications for T2D, we analyzed and replicated genome-wide protein coding variation in a total of 8,227 individuals with T2D and 12,966 individuals without T2D of Latino descent. We identified a novel genetic variant in the IGF2 gene associated with ∼20% reduced risk for T2D. This variant, which has an allele frequency of 17% in the Mexican population but is rare in Europe, prevents splicing between IGF2 exons 1 and 2. We show in vitro and in human liver and adipose tissue that the variant is associated with a specific, allele-dosage–dependent reduction in the expression of IGF2 isoform 2. In individuals who do not carry the protective allele, expression of IGF2 isoform 2 in adipose is positively correlated with both incidence of T2D and increased plasma glycated hemoglobin in individuals without T2D, providing support that the protective effects are mediated by reductions in IGF2 isoform 2. Broad phenotypic examination of carriers of the protective variant revealed no association with other disease states or impaired reproductive health. These findings suggest that reducing IGF2 isoform 2 expression in relevant tissues has potential as a new therapeutic strategy for T2D, even beyond the Latin American population, with no major adverse effects on health or reproduction.
AU - Mercader,JM
AU - Liao,RG
AU - Bell,AD
AU - Dymek,Z
AU - Estrada,K
AU - Tukiainen,T
AU - Huerta-Chagoya,A
AU - Moreno-Macias,H
AU - Jablonski,KA
AU - Hanson,RL
AU - Walford,GA
AU - Moran,I
AU - Chen,L
AU - Agarwala,V
AU - Luisa,Ordonez-Sanchez M
AU - Rodriguez-Guillen,R
AU - Rodriguez-Torres,M
AU - Segura-Kato,Y
AU - Garcia-Ortiz,H
AU - Centeno-Cruz,F
AU - Barajas-Olmos,F
AU - Caulkins,L
AU - Puppala,S
AU - Fontanillas,P
AU - Williams,AL
AU - Bonas-Guarch,S
AU - Hartl,C
AU - Ripke,S
AU - Tooley,K
AU - Lane,J
AU - Zerrweck,C
AU - Martinez-Hernandez,A
AU - Cordova,EJ
AU - Mendoza-Caamal,E
AU - Contreras-Cubas,C
AU - Gonzalez-Villalpando,ME
AU - Cruz-Bautista,I
AU - Munoz-Hernandez,L
AU - Gomez-Velasco,D
AU - Alvirde,U
AU - Henderson,BE
AU - Wilkens,LR
AU - Le,Marchand L
AU - Arellano-Campos,O
AU - Riba,L
AU - Harden,M
AU - Gabriel,S
AU - Abboud,HE
AU - Cortes,ML
AU - Revilla-Monsalve,C
AU - Islas-Andrade,S
AU - Soberon,X
AU - Curran,JE
AU - Jenkinson,CP
AU - DeFronzo,RA
AU - Lehman,DM
AU - Hanis,CL
AU - Bell,GI
AU - Boehnke,M
AU - Blangero,J
AU - Duggirala,R
AU - Saxena,R
AU - MacArthur,D
AU - Ferrer,J
AU - McCarroll,SA
AU - Torrents,D
AU - Knowler,WC
AU - Baier,LJ
AU - Burtt,N
AU - Gonzalez-Villalpando,C
AU - Haiman,CA
AU - Aguilar-Salinas,CA
AU - Tusie-Luna,T
AU - Flannick,J
AU - Jacobs,SBR
AU - Orozco,L
AU - Altshuler,D
AU - Florez,JC
DO - 10.2337/db17-0187
EP - 2914
PY - 2017///
SN - 0012-1797
SP - 2903
TI - A loss-of-function splice acceptor variant in IGF2 is protective for type 2 diabetes
T2 - Diabetes
UR - http://dx.doi.org/10.2337/db17-0187
UR - http://hdl.handle.net/10044/1/78933
VL - 66
ER -
