Polymorphisms in AHI1 are not associated with type 2 diabetes or related phenotypes in Danes: non-replication of a genome-wide association result.
OBJECTIVE
A genome-wide association study recently identified an association between common variants, rs1535435 and rs9494266, in the AHI1 gene and type 2 diabetes. The aim of the present study was to investigate the putative association between these polymorphisms and type 2 diabetes or type 2 diabetes-related metabolic traits in Danish individuals.


METHODS
The previously associated polymorphisms were genotyped in the population-based Inter99 cohort (n=6162), the Danish ADDITION study (n=8428), a population-based sample of young healthy participants (n=377) and in additional type 2 diabetes (n=2107) and glucose-tolerant participants (n=483) using Taqman allelic discrimination. The case-control study involved 4,104 type 2 diabetic patients and 5,050 glucose-tolerant control participants. Type 2 diabetes-related traits were investigated in 17,521 individuals.


RESULTS
rs1535435 and rs9494266 were not associated with type 2 diabetes. Odds ratios (OR) were OR(add) 1.0 (95% C.I. 0.9-1.2; p(add)=0.7) and OR(add) 1.1 (0.9-1.2; p(add)=0.4), respectively, a finding supported by meta-analyses: OR(add) 1.0 (0.9-1.1; p(add)=0.6) and OR(add) 1.0 (0.9-1.1; p(add)=0.6), respectively. Neither rs1535435 nor rs9494266 were consistently associated with any of the tested type 2 diabetes-related metabolic traits.


CONCLUSIONS
Data from large samples of Danish individuals do not support a role for AHI1 rs1535435 nor rs9494266 as major type 2 diabetes variants. This study highlights the importance of independent and well-powered replication studies of the recent genome-wide association scans before a locus is robustly validated as being associated with type 2 diabetes.
Holmkvist
J
J
Steno Diabetes Center, Niels Steensens Vej 1, NLC2.12, 2820 Gentofte, Denmark. chkv@steno.dk
Anthonsen
S
S
Wegner
L
L
Andersen
G
G
Jørgensen
T
T
Borch-Johnsen
K
K
Sandbaek
A
A
Lauritzen
T
T
Pedersen
O
O
Hansen
T
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D033942:Adaptor Proteins, Vesicular Transport; D015992:Body Mass Index; D004261:DNA Replication; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D016002:Discriminant Analysis; D006580:Genetic Carrier Screening; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D010641:Phenotype
C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport