CONTEXT: Krüppel-like factor 11 (KLF11) is a transcription factor of the zinc finger domain family that has been shown to regulate expression of the insulin gene. An initial study reported that a KLF11 variant predicting a Q62R was associated with type 2 diabetes (T2D) in French Caucasians; however, subsequent studies have failed to identify an association between this variant and T2D in subjects from a similar Northern-European ancestry. OBJECTIVE: We sought to determine whether the Q62R or other variants within KLF11 were associated with T2D in Pima Indians, a population with an extremely high prevalence of this disease. DESIGN, SETTING, AND SUBJECTS: KLF11 was sequenced in 24 Pima Indians to identify potentially novel variants. There were 18 variants genotyped in a family-based sample of 1337 Pima Indians to analyze the linkage disequilibrium pattern of this gene and identify representative variants. Four representative variants were further genotyped in a population-based sample of 3501 full-heritage Pima Indians for association analyses. Among these subjects, 413 had undergone metabolic studies when they were nondiabetic to measure traits that predict T2D. RESULTS: Neither the Q62R nor any other common variant in KLF11 was associated with T2D in the Pima population. In addition, no variant was associated with insulin secretion or insulin-stimulated glucose disposal rate. CONCLUSIONS: Common variation in KLF11 variation does not appear to influence the population-based risk for developing T2D among full-heritage Pima Indians. Thus, KLF11 is unlikely to play a major role in the etiology of T2D among this Native American population.
CONTEXT: Krüppel-like factor 11 (KLF11) is a transcription factor of the zinc finger domain family that has been shown to regulate expression of the insulin gene. An initial study reported that a KLF11 variant predicting a Q62R was associated with type 2 diabetes (T2D) in French Caucasians; however, subsequent studies have failed to identify an association between this variant and T2D in subjects from a similar Northern-European ancestry. OBJECTIVE: We sought to determine whether the Q62R or other variants within KLF11 were associated with T2D in Pima Indians, a population with an extremely high prevalence of this disease. DESIGN, SETTING, AND SUBJECTS:KLF11 was sequenced in 24 Pima Indians to identify potentially novel variants. There were 18 variants genotyped in a family-based sample of 1337 Pima Indians to analyze the linkage disequilibrium pattern of this gene and identify representative variants. Four representative variants were further genotyped in a population-based sample of 3501 full-heritage Pima Indians for association analyses. Among these subjects, 413 had undergone metabolic studies when they were nondiabetic to measure traits that predict T2D. RESULTS: Neither the Q62R nor any other common variant in KLF11 was associated with T2D in the Pima population. In addition, no variant was associated with insulin secretion or insulin-stimulated glucose disposal rate. CONCLUSIONS: Common variation in KLF11 variation does not appear to influence the population-based risk for developing T2D among full-heritage Pima Indians. Thus, KLF11 is unlikely to play a major role in the etiology of T2D among this Native American population.
Authors: R L Hanson; M G Ehm; D J Pettitt; M Prochazka; D B Thompson; D Timberlake; T Foroud; S Kobes; L Baier; D K Burns; L Almasy; J Blangero; W T Garvey; P H Bennett; W C Knowler Journal: Am J Hum Genet Date: 1998-10 Impact factor: 11.025
Authors: S Lillioja; D M Mott; M Spraul; R Ferraro; J E Foley; E Ravussin; W C Knowler; P H Bennett; C Bogardus Journal: N Engl J Med Date: 1993-12-30 Impact factor: 91.245
Authors: T Tanahashi; K Shinohara; P Keshavarz; Y Yamaguchi; K Miyawaki; K Kunika; M Moritani; N Nakamura; T Yoshikawa; H Shiota; H Inoue; M Itakura Journal: Diabet Med Date: 2008-01 Impact factor: 4.359
Authors: Roderick C Slieker; Amber A W A van der Heijden; Nienke van Leeuwen; Hailiang Mei; Giel Nijpels; Joline W J Beulens; Leen M 't Hart Journal: Diabetologia Date: 2017-11-20 Impact factor: 10.122