ABSTRACT
AIMS/HYPOTHESIS: To validate the reported association between rs10494366 in NOS1AP (the gene encoding nitric oxide synthase-1 adaptor protein) and the incidence of type 2 diabetes in calcium channel blocker (CCB) users and to identify additional NOS1AP variants associated with type 2 diabetes risk. METHODS: Data from 9 years of follow-up in 9,221 middle-aged white and 2,724 African-American adults free of diabetes at baseline from the Atherosclerosis Risk in Communities study were analysed. Nineteen NOS1AP variants were examined for associations with incident diabetes and fasting glucose levels stratified by baseline CCB use. RESULTS: Prevalence of CCB use at baseline was 2.7% (n = 247) in whites and 2.3% (n = 72) in African-Americans. Among white CCB users, the G allele of rs10494366 was associated with lower diabetes incidence (HR 0.57, 95% CI 0.35-0.92, p = 0.016). The association was marginally significant after adjusting for age, sex, obesity, smoking, alcohol use, physical activity, hypertension, heart rate and electrocardiographic QT interval (HR 0.63, 95% CI 0.38-1.04, p = 0.052). rs10494366 was associated with lower average fasting glucose during follow-up (p = 0.037). No other variants were associated with diabetes risk in CCB users after multiple-testing correction. No associations were observed between any NOS1AP variant and diabetes development in non-CCB users. NOS1AP variants were not associated with diabetes risk in either African-American CCB users or non-CCB users. CONCLUSIONS/INTERPRETATION: We have independently replicated the association between rs10494366 in NOS1AP and incident diabetes among white CCB users. Further exploration of NOS1AP variants and type 2 diabetes and functional studies of NOS1AP in type 2 diabetes pathology is warranted.
Subject(s)
Atherosclerosis/genetics , Calcium Channel Blockers/pharmacology , Calcium Channels/metabolism , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Adult , Black or African American , Black People , Blood Glucose/metabolism , Electrocardiography/methods , Female , Humans , Incidence , Male , Middle Aged , Risk , White PeopleABSTRACT
Pattern recognition techniques--discriminant analysis and principal component analysis--are utilized in selecting the wavelengths for monitoring, by reflectance spectroscopy, color-generating reactions involving uric acid and cholesterol in serum. The data base we used was accumulated by a rapid-scanning reflectance spectrophotometer that measured reflectance at 16 wavelengths every 5 s after the reaction was initiated. The data were then analyzed in multidimensional space mainframe computer with commercial statistical software packages. The most appropriate wavelengths were those that yielded the largest generalized distance between analyte concentration by discriminant analysis and the largest weighting coefficient by principal component analysis. For uric acid, taking the ratio of reflectance measured at two wavelengths instead of at a single wavelength much better separates the clinically significant concentrations. For cholesterol, the initiated. The data were then analyzed in multidimensional space hemoglobin, can be clearly demonstrated y the "pattern" generated with principal component analysis. generalized distance between analyte generalized distance between analyte concentration by discriminant
