Haplotypes failure

Since elucidation of the sequences of the genes encoding the alr a2, and subtypes of adrenoceptors, it has become clear that there are relatively common genetic polymorphisms for many of these receptor subtypes in humans. Some of these may lead to changes in critical amino acid sequences that have pharmacologic importance. Often, distinct polymorphisms occur in specific combination termed haplotypes. Some of these polymorphisms have been consistently shown to alter the susceptibility to diseases such as heart failure, to alter the propensity of a receptor to desensitize, and to alter therapeutic responses to drugs in diseases such as asthma. This remains an area of active research because studies have reported inconsistent results as to the pathophysiologic importance of some polymorphisms. 

Sobell JL, Richard C, Wirshing DA, Heston LL. Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians. Am J Med Genet B Neuropsychiatr Genet 2005 139(l) 23-27. 

Datta SR, McQuillin A, Puri V, Choudhury K, Thirumalai S, et al. 2007. Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystro-brevin-binding protein 1 (DTNBP1) locus and schizophrenia. Behav Brain Funct 3 50. 

In addition to an efficient-metabolism phenotype, variant alleles encode a poor-metabolism phenotype, with low or no enzyme activity towards a particular drug. On occasion, because of one or more gene dupH-cations, a variant genotype might involve a very high ultra-metabolism phenotype resulting in treatment failure and toxic effects. Similarly, rates of detoxification and sometimes of metabolic activation of environmental chemicals can be strikingly different between individuals with different CYP haplotypes. Of particular... 

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