AIMS/HYPOTHESIS: Insulin clearance is a highly heritable trait, for which few quantitative trait loci have been discovered. We sought to determine whether validated type 2 diabetes and/or glycaemic trait loci are associated with insulin clearance. METHODS: Hyperinsulinaemic-euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329 participants in 329 families. The Metabochip was used to fine-map about 50 previously identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA1c. This resulted in 17,930 variants, which were tested for association with clamp-derived insulin clearance via meta-analysis of the two cohorts. RESULTS: In the meta-analysis, 38 variants located within seven loci demonstrated association with insulin clearance (p < 0.001). The top signals for each locus were rs10241087 (DGKB/TMEM195 [TMEM195 also known as AGMO]) (p = 4.4 × 10(-5)); chr1:217605433 (LYPLAL1) (p = 3.25 × 10(-4)); rs2380949 (GLIS3) (p = 3.4 × 10(-4)); rs55903902 (FADS1) (p = 5.6 × 10(-4)); rs849334 (JAZF1) (p = 6.4 × 10(-4)); rs35749 (IGF1) (p = 6.7 × 10(-4)); and rs9460557 (CDKAL1) (p = 6.8 × 10(-4)). CONCLUSIONS/ INTERPRETATION: While the majority of validated loci for type 2 diabetes and related traits do not appear to influence insulin clearance in Hispanics, several of these loci do show evidence of association with this trait. It is therefore possible that these loci could have pleiotropic effects on insulin secretion, insulin sensitivity and insulin clearance.
AIMS/HYPOTHESIS: Insulin clearance is a highly heritable trait, for which few quantitative trait loci have been discovered. We sought to determine whether validated type 2 diabetes and/or glycaemic trait loci are associated with insulin clearance. METHODS: Hyperinsulinaemic-euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329 participants in 329 families. The Metabochip was used to fine-map about 50 previously identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA1c. This resulted in 17,930 variants, which were tested for association with clamp-derived insulin clearance via meta-analysis of the two cohorts. RESULTS: In the meta-analysis, 38 variants located within seven loci demonstrated association with insulin clearance (p < 0.001). The top signals for each locus were rs10241087 (DGKB/TMEM195 [TMEM195 also known as AGMO]) (p = 4.4 × 10(-5)); chr1:217605433 (LYPLAL1) (p = 3.25 × 10(-4)); rs2380949 (GLIS3) (p = 3.4 × 10(-4)); rs55903902 (FADS1) (p = 5.6 × 10(-4)); rs849334 (JAZF1) (p = 6.4 × 10(-4)); rs35749 (IGF1) (p = 6.7 × 10(-4)); and rs9460557 (CDKAL1) (p = 6.8 × 10(-4)). CONCLUSIONS/ INTERPRETATION: While the majority of validated loci for type 2 diabetes and related traits do not appear to influence insulin clearance in Hispanics, several of these loci do show evidence of association with this trait. It is therefore possible that these loci could have pleiotropic effects on insulin secretion, insulin sensitivity and insulin clearance.
Authors: A H Xiang; S P Azen; L J Raffel; S Tan; L S Cheng; J Diaz; E Toscano; P C Henderson; H N Hodis; W A Hsueh; J I Rotter; T A Buchanan Journal: Circulation Date: 2001-01-02 Impact factor: 29.690
Authors: D Altshuler; J N Hirschhorn; M Klannemark; C M Lindgren; M C Vohl; J Nemesh; C R Lane; S F Schaffner; S Bolk; C Brewer; T Tuomi; D Gaudet; T J Hudson; M Daly; L Groop; E S Lander Journal: Nat Genet Date: 2000-09 Impact factor: 38.330
Authors: Otto Tschritter; Andreas Fritsche; Norbert Stefan; Michael Haap; Claus Thamer; Oliver Bachmann; Dominik Dahl; Elke Maerker; Anna Teigeler; Fausto Machicao; Hans Häring; Michael Stumvoll Journal: Metabolism Date: 2003-06 Impact factor: 8.694
Authors: Hong Soon Kang; Liang-Yu Chen; Kristin Lichti-Kaiser; Grace Liao; Kevin Gerrish; Carl D Bortner; Humphrey H-C Yao; Edward M Eddy; Anton M Jetten Journal: Stem Cells Date: 2016-07-11 Impact factor: 6.277
Authors: Brunilda Balliu; Ivan Carcamo-Orive; Michael J Gloudemans; Daniel C Nachun; Matthew G Durrant; Steven Gazal; Chong Y Park; David A Knowles; Martin Wabitsch; Thomas Quertermous; Joshua W Knowles; Stephen B Montgomery Journal: Am J Hum Genet Date: 2021-09-27 Impact factor: 11.025
Authors: Mark O Goodarzi; Nicholette D Palmer; Jinrui Cui; Xiuqing Guo; Yii-Der I Chen; Kent D Taylor; Leslie J Raffel; Lynne E Wagenknecht; Thomas A Buchanan; Willa A Hsueh; Jerome I Rotter Journal: J Clin Endocrinol Metab Date: 2020-04-01 Impact factor: 5.958
Authors: Vincent A Laufer; Hemant K Tiwari; Richard J Reynolds; Maria I Danila; Jelai Wang; Jeffrey C Edberg; Robert P Kimberly; Leah C Kottyan; John B Harley; Ted R Mikuls; Peter K Gregersen; Devin M Absher; Carl D Langefeld; Donna K Arnett; S Louis Bridges Journal: Hum Mol Genet Date: 2019-03-01 Impact factor: 6.150