The mutation in question is a small deletion in a gene that encodes a protein called CCR5, which was identified in 1996 as a co-receptor used by HIV to infect cells. Individuals with two copies of this mutation (CCR5delta32) are highly resistant to HIV infection, even when repeatedly exposed to the virus.

This resistance was the theoretical basis for the development of therapeutic CCR5 inhibitors, several of which are now in clinical trials, for the treatment of patients with HIV. CCR5 seemed like an ideal drug target, as people missing the receptor were healthy and no diseases or infections had been shown to be more frequent or severe in individuals carrying the CCR5delta32 mutation.

But new evidence suggests that the lack of CCR5 is not completely innocuous. Philip Murphy and his colleagues at the National Institute of Allergy and Infectious Diseases (Bethesda, MD) recently showed that infection with WNV -- a mosquito-borne virus that caused a1999 outbreak of fatal encephalitis in the US -- was uniformly fatal in mice that lack CCR5.

This finding prompted Murphy and his colleagues to look for the CCR5delta32 mutation in patients in the US who were diagnosed with WNV infections. They now report that individuals with two copies of CCR5delta32 were more frequent among WNV patients than in the general population, suggesting that the lack of CCR5 puts people at risk for developing clinical WNV infections. In mice, the lack of CCR5 prevents protective immune cells from gaining access to the brain where they can fight off the infection. It remains to be seen whether the same mechanism is at play in humans.

This study might raise a red flag for the use of CCR5 inhibitors in HIV-infected patients -- at least in areas endemic for WNV -- as such inhibitors might increase the recipients' vulnerability to severe WNV infection.

jem/

Genetic association studies are inconclusive with regard to the best genetic candidates in the smoking cessation field The responsibilities of general adult psychiatrists, substance misuse service professionals and general practitioners are already significant, without the additional burden of informing themselves about, and providing counselling on, gene-based therapies The cost implications for the NHS of this added duty is of concern Current privacy laws within the UK fail to protect patients from the misuse of genetic information. Many European countries have laws preventing insurers and prospective employers from gaining access to an individual's genetic profile. When patients spend money on a genetic test for smoking cessation, they are inadvertently generating information about their risk of predisposition to developing or possessing a number of other stigmatising conditions, such as alcohol or cocaine addiction, or pathological gambling The majority of people who attempt to give up smoking using genetic tests will fail -success rates are as low as 20% in a year Information provided to patients from the test may mislead them into thinking they have a particularly virulent or 'genetic' form of addiction, and are never going to be able to give up.

The authors of the editorial conclude that more research is needed to verify the usefulness of genetic tests for smoking cessation, especially among general medical and psychiatric patients.

Until there is greater understanding of the genetic influences in nicotine addiction, patients being cared for in psychiatric services are best advised to avoid such tests.

rcpsych.ac