title: Identifying genetic susceptibilities to diabetes-related complications among individuals at low risk of complications: An application of tree-structured survival analysis.
abstract: The authors hypothesized that genetic predisposition to diabetes complications would be more evident among low-risk individuals and aimed to identify genes related to developing complications (confirmed distal symmetric polyneuropathy, overt nephropathy, or coronary artery disease) in low-risk groups. Participants in the Pittsburgh, Pennsylvania, Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes, first seen in 1986-1988 (mean age, 28 years; diabetes duration, 19 years), were reexamined biennially for 10 years. For each complication, subgroups with the lowest disease risk were identified by using tree-structured survival analysis, and 15 candidate genes were compared between subjects with and without complications. In the group with the lowest incidence of confirmed distal symmetric polyneuropathy (n = 123), confirmed distal symmetric polyneuropathy risk increased fivefold for those with the eNOS GG genotype (p < 0.05). In the group with the lowest risk of overt nephropathy (n = 340), the ACE D polymorphism increased overt nephropathy risk twofold (p = 0.05), whereas a protective effect was observed for the LIPC CC genotype (p < 0.05). In the group with the lowest incidence of coronary artery disease (n = 331), the MTHFR CC genotype increased coronary artery disease risk threefold (p < 0.05). Tree-structured survival analysis may help identify genetic predispositions among individuals who, despite low risk, develop diabetes-related complications.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.forename: Yuefang
authors.initials: Y
authors.lastname: Chang
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000328:Adult; D048909:Diabetes Complications / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012306:Risk; D016019:Survival Analysis
chemical_list: C504173:LIPC protein, human; D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008049:Lipase; D007703:Peptidyl-Dipeptidase A