Search of type 2 diabetes susceptibility gene on chromosome 20q.
Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4alpha (HNF4A) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP, with an estimated odds ratio of 1.73 (95% CI 1.30-2.31) (P=0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study.
Takeuchi
F
F
Department of Medical Ecology and Informatics, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Yanai
K
K
Inomata
H
H
Kuzuya
N
N
Kajio
H
H
Honjo
S
S
Takeda
N
N
Kaburagi
Y
Y
Yasuda
K
K
Shirasawa
S
S
Sasazuki
T
T
Kato
N
N
D000209:Acute-Phase Proteins / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D051557:Hepatocyte Nuclear Factor 4; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein; C496592:HNF4A protein, human