@article {1109, title = {Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease.}, journal = {J Med Genet}, volume = {47}, year = {2010}, month = {2010 Jan}, pages = {1-7}, abstract = {

BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD.

METHODS: The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus.

RESULTS: The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95\% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95\% CI 1.29 to 2.76).

CONCLUSION: This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans.

}, keywords = {African Americans, Aged, Ankle Brachial Index, Chromosome Mapping, Chromosomes, Human, Pair 11, Female, Genetic Loci, Genotype, Humans, Male, Odds Ratio, Peripheral Vascular Diseases, Polymorphism, Single Nucleotide}, issn = {1468-6244}, doi = {10.1136/jmg.2008.064808}, author = {Scherer, M L and Nalls, M A and Pawlikowska, L and Ziv, E and Mitchell, G and Huntsman, S and Hu, D and Sutton-Tyrrell, K and Lakatta, E G and Hsueh, W-C and Newman, A B and Tandon, A and Kim, L and Kwok, P-Y and Sung, A and Li, R and Psaty, B and Reiner, A P and Harris, T} } @article {1549, title = {A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.}, journal = {Clin Pharmacol Ther}, volume = {91}, year = {2012}, month = {2012 May}, pages = {896-904}, abstract = {

An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95\% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17\%) than in those receiving atorvastatin (0\%, OR infinity; 95\% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8.

}, keywords = {Adverse Drug Reaction Reporting Systems, Aged, Aged, 80 and over, Aryl Hydrocarbon Hydroxylases, Case-Control Studies, Cytochrome P-450 CYP2C8, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP3A Inhibitors, Drug Interactions, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Male, Platelet Aggregation Inhibitors, Pyridines, Rhabdomyolysis, Ticlopidine}, issn = {1532-6535}, doi = {10.1038/clpt.2011.295}, author = {Floyd, J S and Kaspera, R and Marciante, K D and Weiss, N S and Heckbert, S R and Lumley, T and Wiggins, K L and Tamraz, B and Kwok, P-Y and Totah, R A and Psaty, B M} }