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Articles by L. A Lange
Total Records ( 2 ) for L. A Lange
  L. A Lange , A. B Kampov Polevoy and J. C. Garbutt

Aim: We tested the hypothesis that high novelty seeking (NS; a trait that promotes experimentation) and hedonic response to sweet taste (a trait that may reflect processing of hedonic stimuli) act independently to increase the risk for having alcohol-related problems in young adults. Methods: The study was conducted in 158 healthy subjects (age 20–25 years) with no lifetime history of alcohol and/or drug abuse/dependence. NS was evaluated using the Tridimensional Personality Questionnaire. Pleasurable response to sweet taste was tested, using a sweet taste test to identify sweet likers (SL; those preferring the strongest offered sucrose solution) and sweet dislikers (SDL; those preferring weaker sucrose solutions). Results: NS score, but not SL/SDL status, was positively correlated with drinks per month (P = 0.0054) and drinks per drinking day (P = 0.021). When tested individually, both NS and SL/SDL status predict having alcohol-related problems (NS: odds ratio [OR] = 5.3, P = 0.0016 and SL/SDL: OR = 5.8, P = 0.0001) with an OR similar to positive family history of alcoholism status (OR = 5.7, P = 0.0007). The combination of SL status and high NS score (greater than gender-specific 70th percentile) greatly increased the estimated odds of having alcohol-related problems (OR 27.5, P < 0.0001). Conclusions: These results support the hypothesis that high NS and SL phenotypes are independently associated with risk of alcohol-related problems. The combination of both phenotypes greatly increases the likelihood of alcohol-related problems. Although confirmation is necessary, this suggests that these phenotypes could contribute to improved methods to assess risk for alcohol-related problems and provide additional insight into processes underlying progression to alcohol-related problems.

  A. P Reiner , M. D Gross , C. S Carlson , S. J Bielinski , L. A Lange , M Fornage , N. S Jenny , J Walston , R. P Tracy , O. D Williams , D. R Jacobs and D. A. Nickerson

Background— The transcription factor hepatocyte nuclear factor (HNF)-1 regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1 gene (HNF1A) were recently associated with plasma C-reactive protein and -glutamyl transferase concentration in middle-aged to older European Americans (EA).

Methods and Results— We assessed whether common variants of HNF1A are associated with C-reactive protein, -glutamyl transferase, and other atherosclerotic and metabolic risk factors, in the large, population-based Coronary Artery Risk Development in Young Adults Study of healthy young EA (n=2154) and African American (AA; n=2083) adults. The minor alleles of Ile27Leu (rs1169288) and Ser486Asn (rs2464196) were associated with 0.10 to 0.15 standard deviation units lower C-reactive protein and -glutamyl transferase levels in EA. The same HNF1A coding variants were associated with higher low-density lipoprotein cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated the associations between HNF1A coding variants and C-reactive protein, fibrinogen, low-density lipoprotein cholesterol, and renal function in a second population-based sample of EA adults 65 years and older from the Cardiovascular Health Study. The HNF1A Ser486Asn and/or Ile27Leu variants were also associated with increased risk of subclinical coronary atherosclerosis in Coronary Artery Risk Development in Young Adults and with incident coronary heart disease in Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less common in AA than in EA. There was little evidence of association between HNF1A genotype and atherosclerosis-related phenotypes in AA.

Conclusions— Common polymorphisms of HNF1A seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.

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