Nic picks

The patch works best for women with the CT or TT variant of the dopamine D2 receptor while CC women are out of luck

By D Ward Rivers

Some research can leave you feeling more confused about a subject than you were before you read it. A study published March 19 in the online version of British Medical Journal about nicotine patches and gender certainly falls into this category.

Few clinical interventions appear as straightforward on the surface as the nicotine patch. Cigarettes provide nicotine, patches provide nicotine, ergo patches can replace cigarettes. If only things were that simple.

In recent years, it's been postulated, partly on the basis of animal research, that nicotine addiction works differently in males and females. There are also different genotypes of the dopamine D2 receptor that's blamed for a large part of tobacco addiction.

This study followed up 752 people who had participated in a nicotine patch tobacco-quitting study in the early 1990s. The researchers divided them by sex and dopamine D2 receptor genotype. Sixty percent of the subjects had the CC genotype, while 40% carried the variant T allele, producing a genotype of either CT or TT.

There was just one outcome measure � had they managed to quit? The honesty of subjects' responses was verified by measuring concentrations of plasma cotinine � the chemical breakdown of nicotine in the body. The first goal of the researchers was to establish whether dopamine D2 genotype influenced the effectiveness of patches as a quitting aid. In women, it clearly did. Among women with the slightly rarer CT or TT genotypes, those wearing nicotine patches were three times as likely to quit and stay off the smokes as those using a placebo patch. Among the 60% of women with the CC genotype, it made no difference whether the patches were real or not.

CT and TT women with real nicotine patches had the highest success rate, followed by CC genotype women regardless of patch type while CT or TT women with placebo patches came in last.

Clearly, in women the variant T allele increases the importance of the dopamine D2 receptor's role, making these women ideal candidates for nicotine therapy.

Unfortunately, everything turned upside down when the men were considered. The authors wrote that, "No significant relation between genotype and patch effectiveness was seen for men." Strictly speaking, that is true, since significance is achieved when the P value drops below 0.05. But there was a string of results showing that men with the CC genotype who had used real patches were far more successful at staying tobacco free after the first year than those who had worn placebo patches.

At P=0.06, these results may not quite reach technical significance, but there is a pattern that the authors are at a loss to explain. As they put it: "In men with CC genotype an apparent trend in effectiveness was in an implausible direction, the patches being most effective long after therapy had stopped."