Search for type 2 diabetes susceptibility genes on chromosomes 1q, 3q and 12q.
To systematically evaluate genetic susceptibility to type 2 diabetes (T2D) in "candidate" regions on chromosomes 1q, 3q and 12q, we examined disease association by using a total of 2,083 SNPs in two-step screening; a screening panel comprised 473 cases and 285 controls and an extended (or combined) panel involved 658 cases and 474 controls. For the total interval screened (40.9 Mb), suggestive evidence of association was provided for several annotated gene loci. For example, in the MCF2L2 gene on 3q, a significant association (a nominal P value of 0.00009) was observed when logistic regression analysis was performed for three associated SNPs (rs684846, rs35069869 and rs35368790) that belonged to different LD groups. Also, in the SLC15A4 gene on 12q, rs3765108 showed a marginally significant association with an overall estimated odds ratio of 0.79 (P=0.001). No significant association was found for known candidate gene loci on 3q, such as ADIPOQ and IGF2BP2. Using the available samples, we have observed disease associations of SNPs derived from two novel gene loci in the Japanese population through high-density searches of diabetes susceptibility in three chromosomal regions. Independent replication will clarify the etiological relevance of these genomic loci to T2D.
Takeuchi
F
F
Department of Medical Ecology and Informatics, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Ochiai
Y
Y
Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
Serizawa
M
M
Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
Yanai
K
K
Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
Kuzuya
N
N
Division of Metabolic Diseases, The Hospital, International Medical Center of Japan, Tokyo, Japan.
Kajio
H
H
Division of Metabolic Diseases, The Hospital, International Medical Center of Japan, Tokyo, Japan.
Honjo
S
S
Division of Metabolic Diseases, The Hospital, International Medical Center of Japan, Tokyo, Japan.
Takeda
N
N
Division of Ophthalmology, The Hospital, International Medical Center of Japan, Tokyo, Japan.
Kaburagi
Y
Y
Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Yasuda
K
K
Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Shirasawa
S
S
Department of Pathology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Sasazuki
T
T
International Medical Center of Japan, Tokyo, Japan.
Kato
N
N
Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan. nokato@ri.imcj.go.jp.
D044466:Asian People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008126:Lod Score; D016015:Logistic Models; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C491359:SLC15A4 protein, human