Association analysis of Krüppel-like factor 11 variants with type 2 diabetes in Pima Indians.
BACKGROUND
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.


METHODS
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.
Ma
Lijun
L
Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Phoenix, Arizona 85004, USA.
Hanson
Robert L
RL
Que
Lorem N
LN
Mack
Janel L
JL
Franks
Paul W
PW
Infante
Aniello M
AM
Kobes
Sayuko
S
Bogardus
Clifton
C
Baier
Leslie J
LJ
D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; C115117:KLF11 protein, human; D012097:Repressor Proteins