Genetic variation in adiponectin receptor 1 and adiponectin receptor 2 is associated with type 2 diabetes in the Old Order Amish.
Adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) are newly identified receptors for adiponectin, an adipocytokine with anti-inflammatory and insulin-sensitizing properties. We screened for polymorphisms by performing sequence analysis on all eight exons, splice junctions, and approximately 2 kb of the 5' flanking regions of each receptor. We detected 5 single nucleotide polymorphisms (SNPs) in ADIPOR1 and 16 SNPs in ADIPOR2. We genotyped these SNPs in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT) (n = 139), and normal glucose tolerance (n = 342) to test for association with type 2 diabetes. Three intronic SNPs in ADIPOR1 were significantly associated with type 2 diabetes (P = 0.014-0.007; odds ratio [OR] 1.61-1.65) and in high linkage disequilibrium (r2 = 0.97-1.0). In ADIPOR2, we found that five SNPs delineated one large haplotype block (r2= 0.9-1.0) spanning >98 kb of the gene and promoter region, which was strongly associated with the combined type 2 diabetes/IGT trait (P < or = 0.001; OR 1.64-1.71). To our knowledge, these data provide the first evidence for association between variation in the adiponectin receptors and type 2 diabetes.
Damcott
Coleen M
CM
Division of Endocrinology, Diabetesand Nutrition, University of Maryland School of Medicine, 660 West Redwood St., Room 494, Baltimore, MD 21201, USA.
Ott
Sandra H
SH
Pollin
Toni I
TI
Reinhart
Laurie J
LJ
Wang
Jian
J
O'connell
Jeffrey R
JR
Mitchell
Braxton D
BD
Shuldiner
Alan R
AR
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics*; D012016:Reference Values; D044465:White People / Q000235:genetics
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D001786:Blood Glucose; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface