Association of Ob-R gene polymorphism and insulin resistance in Japanese men.
Leptin and its receptors are known to play a role in glucose metabolism. We succeeded in cloning human Ob-R cDNA and revealed 7 single nucleotide polymorphisms (SNPs) (Lys109Arg, Arg223Gln, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the coding region of Ob-Rb. Although these 7 SNPs were not associated with an obese phenotype, several studies have reported that some of them were associated with impaired glucose metabolism. To clarify whether the Arg223Gln and A3057G (Pro1019Pro) polymorphisms influence glucose metabolism in Japanese, 696 Japanese men were genotyped. Individually, the Arg223Gln and the A3057G polymorphisms were not associated with the glucose metabolic parameters. No associations were found between haplotype and clinical parameters. However, in 327 subjects with normal glucose tolerance (NGT), the subjects with Arg/Gln or Gln/Gln + A/A haplotype showed significantly higher serum insulin levels and homeostasis model assessment (HOMA) index than those with Arg/Arg + A/A haplotype and Arg/Gln or Gln/Gln + A/G or G/G haplotype. The subjects with Arg/Gln or Gln/Gln + A/A haplotype showed a significantly lower fasting glucose to insulin (GI) ratio than those with Arg/Arg + A/A haplotype. These results suggest that the Ob-R gene may serve as a modifier gene for insulin resistance in Japanese men.
Takahashi-Yasuno
Akiko
A
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Masuzaki
Hiroaki
H
Miyawaki
Takashi
T
Matsuoka
Naoki
N
Ogawa
Yoshihiro
Y
Hayashi
Tatsuya
T
Hosoda
Kiminori
K
Yoshimasa
Yasunao
Y
Inoue
Gen
G
Nakao
Kazuwa
K
D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology; D005787:Gene Frequency; D018149:Glucose Intolerance / Q000235:genetics; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin