Type 2 diabetes susceptibility genes on chromosome 1q21-24.
Type 2 diabetes (T2D) has been linked to chromosome 1q21-24 in multiple samples, including a Utah family sample. Variants in 13 of the numerous candidate genes in the 1q region were tested for association with T2D in a Utah case-control sample. The most promising, 19 variants in 6 candidates, were genotyped on the Utah family sample. Herein, we tested the 19 variants individually and in pairs for an effect on T2D risk in family members using a logistic regression model that accounted for gender, age, and BMI and attributed residual genetic effects to a polygenic component. Seven variants increased risk significantly through 5 pairs of interactions. The significant variant pairs were apolipoprotein A-II (APOA2) rs6413453 interacting with calsequestrin 1 (CASQ1) rs617698, dual specificity phosphatase 12 (DUSP12) rs1503814, and retinoid X receptor gamma (RXRG) rs10918169, a poly-T insertion-deletion polymorphism in liver pyruvate kinase (PKLR) interacting with APOA2 rs12143180, and DUSP12 rs1027702 interacting with RXRG rs10918169. Genotypes of these 5 variant pairs accounted for 25.8% of the genetic variance in T2D in these pedigrees.
Hasstedt
S J
SJ
Department of Human Genetics, University of Utah, 15 N. 2030 E., Salt Lake City, UT 84112, USA. sandy@genetics.utah.edu
Chu
W S
WS
Das
S K
SK
Wang
H
H
Elbein
S C
SC
D000367:Age Factors; D000704:Analysis of Variance; D016633:Apolipoprotein A-II / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D002155:Calsequestrin; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D008957:Models, Genetic; D010375:Pedigree; D011110:Polymorphism, Genetic; D047491:Retinoid X Receptor gamma / Q000235:genetics; D012737:Sex Factors; D014589:Utah
C115794:APOA2 protein, human; D016633:Apolipoprotein A-II; C503129:CASQ1 protein, human; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; D024101:Mitochondrial Proteins; D047491:Retinoid X Receptor gamma; C489855:dual specificity phosphatase 12; D054637:Dual-Specificity Phosphatases