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Study Suggests Genotype Improves Response to NRIs


A study published in early October on the genetics of response to antidepressants suggests that a particular genotype can dull the efficacy of selective serotonin reuptake inhibitors while improving a patient’s response to less-popular norepinephrine reuptake inhibitors, or NRIs.

 Published in the Journal of the American Medical Association, the study followed 241 Korean patients being treated for depression and links variants in their norepinephrine transporter and serotonin transporter genes with how they respond to one NRI and two SSRIs.

Apparently ethnicity plays an important role in one of the polymorphisms: according to the study authors, one variant of the serotonin transporter gene produces diametrically opposite responses in East Asians and Caucasians, a finding the same group originally reported in 2000.

The implications of the research are “huge for clinical practice and for the market in antidepressant drugs,” says Bernard Carroll, scientific director of the Pacific Behavioral Research Foundation and study author.

“If this genotyping is taken up in clinical services, then the use of [first-line] SSRI drugs … to treat depression will probably be cut in half, if not more,” says Carroll, who is also former chairman of psychiatry at Duke University and former chairman of the US Food and Drug Administration advisory committee for psychiatric drugs.

The study, led by author Hyeran Kim of Samsung Medical Center in Seoul, South Korea, has “added another dimension” to understanding how norepinephrine transporters affect the efficacy of antidepressant drugs, “and now it makes a lot more sense,” says Dennis O’Kane, director of the Nucleotide Polymorphism Laboratory at the Mayo Clinic in Rochester, Minn. “The Samsung group has made a great contribution to pharmacogenetics by getting this study carried out.”

The findings could trigger pharmacogenomic testing of transporter genes to guide antidepressant treatment “within two to three years,” assuming the Korean study is replicated, O’Kane says.

— Chris Womack



US Patent 7,115,726. Haplotype structures of chromosome 21. Inventors: David Cox and Deana Arnold. Assignee: Perlegen Sciences. Issued: October 3, 2006. The invention “includes the use of any of the polymorphisms, SNP haplotype blocks or SNP haplotype patterns,” according to the patent abstract. In one embodiment, “susceptibility to a phenotype resulting from an allele or marker in linkage disequilibrium with such polymorphic forms is evaluated.” Novel therapeutic and diagnostic compounds and methods are also disclosed.  

US Patent 7,108,978. Method for detecting a propensity of an individual to respond effectively to treatment of interferon-alpha and ribavirin combined therapy. Inventors: Jui-Lin Chen, Yuchi Hwang, Min-Pey Ding, Wen-Pi Chu, Shu-Ching Wang, Kuei-Ling Belinda Chen, et al. Assignee: Vita Genomics. Issued: September 19, 2006. Covers isolated polynucleotides that include sequences from the genomic region around the gene CD 81. These polynucleotides “include polymorphisms associated with treatment response of HCV patients to interferon-alpha and ribavirin combined therapy,” according to the patent’s abstract.



Boston University and Howard University researchers will use Affymetrix arrays to perform the first genome-wide scan of an African-American cohort for genes associated with obesity and other metabolic disorders. The data will be included within the Affymetrix Control Program, which provides free public access to control data for population genomics projects.  

The US National Institutes of Health plans to reallocate at least $100 million from the Roadmap Initiative to help pay for a new consortium that will bring together 60 institutions using genomic and other technologies to improve clinical research.  

Whatman said that its Combichip multiplex protein biochip, indicated for autoimmune diseases, has received CE registration as an in vitro diagnostic and will be available to reference labs as a CE-marked IVD kit.  

Clinical Data has aligned itself with PharmaCare, the fourth-largest pharmacy benefit manager in the US. Terms of the deal call for Clinical Data unit PGxHealth to use its molecular diagnostic services to help PharmaCare identify patients at risk for being improperly dosed for warfarin or for developing a potentially fatal adverse event when on clozapine.  

Pfizer-funded researchers at the Oregon Health and Science University in Portland have identified mutations that suggest Sutent, a Pfizer drug, may perform better than Novartis’ Gleevec in some cases.



$2 million

The US National Human Genome Research Institute will give the Genetics and Public Policy Center $2 million over two years to conduct a pilot “public discussion” in anticipation of large population studies on how genes and the environment affect health

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