title: The haptoglobin 1 allele correlates with white matter hyperintensities in middle-aged adults with type 1 diabetes.
abstract: Although the haptoglobin (Hp) 1-1 genotype is associated with a lower coronary artery disease (CAD) risk in diabetes, we recently reported an increased stroke incidence in type 1 diabetes with Hp 1-1. We, thus, evaluated differences in earlier brain vascular abnormality markers by Hp using neuroimaging. Neuroimaging was completed in 94 participants of the Pittsburgh Epidemiology of Diabetes Complications study with Hp genotyping available (mean age, 49; duration, 41 years). White matter hyperintensities (WMH) volume, lacunar infarcts, and gray matter atrophy were quantified. Sixteen percent were homozygous for Hp 1 and 43% for Hp 2. A significant trend toward increased WMH was observed with greater duration and the number of Hp 1 alleles. Associations were strongest for the interhemispheric connecting fibers of the corpus callosum. Allowing for duration, sex, waist-to-hip ratio, HbA1c, systolic blood pressure, and lipids in models with backward elimination, results were similar. No significant differences by Hp were noted for atrophy or lacunar infarcts. Consistent with its direct association with stroke, the Hp 1-1 genotype is associated with higher WMH in this population. Further, including mechanistic, studies on the role of the Hp genotype in cerebrovascular disease and the implications for worsening cognitive function are needed.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA costacout@edc.pitt.edu.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Howard
authors.initials: H
authors.lastname: Aizenstein
authors.affiliation: Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Mettenburg
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Karen
authors.initials: K
authors.lastname: Nunley
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000235:genetics; D066127:White Matter / Q000473:pathology*
chemical_list: D005819:Genetic Markers; D006242:Haptoglobins