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FAT MASS AND OBESITY-ASSOCIATED
(FTO) GENE AND ALCOHOL INTAKE
In a recent issue of Addiction, Sobczyk-Kopciol et al. [1]
reported an association between the first intron tagging
variant rs9939609 in the obesity-predisposing fat mass
and obesity-associated (FTO) gene (OMIM no. 610966)
and both alcohol consumption and alcohol dependence. Interestingly, the genotype generally associated
with elevated risk of obesity [2], acute coronary syndrome [3], some types of cancer [4], end-stage renal
disease [5] or overall mortality [6] [in all cases at least
partially independently on body mass index (BMI)] was
associated with lower ethanol consumption, and was less
common in alcohol-dependent individuals compared to
healthy controls.
Despite the large number of individuals included
(6584), an important limitation of the original study [1]
is the lack of the confirmatory study. Even large studies
are prone to type I error (false positive), and their results
need to be replicated [7,8].
To confirm the results by Sobczyk-Kopciol et al. [1],
we analysed self-reported alcohol intake (recorded in
a standardized interview) and the first intron tagging
single nucleotide polymorphisms (SNPs) (rs17817449 or
rs9939609; both occur in almost 100% linkage disequilibrium [9]) in three large independent cohorts. We used
the Czech post-MONItoring of trends and determinants
in Cardiovascular disease (MONICA) study (2559 individuals, examined twice within 3 years) [9], the Czech
part of the Health, Alcohol and Psychosocial factors In
Eastern Europe (HAPIEE) study (6681 individuals) [10],
and a study of the self-contained population of 948
Sorbs in Germany [11]. Finally, 201 Czech patients with
alcoholic liver cirrhosis were also genotyped. Data were
analysed using logistic regression with the additive mode
of inheritance and adjustment for age and gender.
The FTO genotype and allele frequencies did not differ
significantly between our three cohorts (0.42–0.43 of
the minor allele) and the study by Sobczyk-Kopciol
et al. [1] (0.45). We detected no significant effect of
rs9939609 or rs17817449 on alcohol intake in any of
the studies; the P-values were 0.47 (0.51 in the second
survey) in the Czech post-MONICA study, 0.37 in the
Czech HAPIEE study and 0.82 in the Sorbs study. For
example, in the Czech HAPIEE study, the largest of our
replication samples, the mean (⫾ standard deviation)
alcohol intakes (in grams) in the last week in CC, CT and
TT carriers were 174 (⫾201), 187 (⫾214) and 177
Addiction © 2012 Society for the Study of Addiction
1185..1187
(⫾184), respectively (P = 0.92), in males and 38 (⫾70),
41 (⫾72) and 43 (⫾77), respectively (P = 0.12), in
females. There were no statistically significant differences
in the frequencies of the individual FTO genotypes in
pooled data of the Czech cohorts (n = 9148, CC = 18.7%,
CT = 48.3%, TT = 33.0%) and in patients with alcoholic
cirrhosis (n = 201, CC = 13.9%, CT = 53.7%, TT =
32.3%), P = 0.16, although the pattern of results was
similar to the results by Sobczyk-Kopciol et al. [1].
In summary, we were unable to replicate the association between the FTO 1st intron tagging SNPs and
alcohol consumption in any of the confirmatory samples.
We conclude that 1st intron FTO tagging SNPs are
unlikely to be major and general genetic determinants of
total alcohol intake/alcohol consumption.
Acknowledgements
This study was supported by project no. 00023001
(IKEM, CR) and by the Welcome Trust, UK (064947,
081081) and by NIA (RO1 AG23522).
Declarations of interest
None.
JAROSLAV A. HUBACEK 1 , VERA ADAMKOVA 1 ,
DANA DLOUHA 1 , MILAN JIRSA 1 , JAN ŠPERL 1 ,
ANKE TÖNJES 2 , PETER KOVACS 2 , HYNEK PIKHART 3 ,
ANNE PEASEY 3 & MARTIN BOBAK 3
Institute for Clinical and Experimental Medicine, Videnska
1958/9, Prague 4, 14021, Czech Republic1,
Medical University of Leipzig, Leipzig, Germany2 and
Department of Epidemiology and Public Health,
University College London, London, UK.3
E-mail: jahb@ikem.cz
References
1. Sobczyk-Kopciol A., Broda G., Wojnar M., Kurjata P.,
Jakubczyk A., Klimkiewicz A. et al. Inverse association of
the obesity predisposing FTO rs9939609 genotype with
alcohol consumption and risk for alcohol dependence.
Addiction 2011; 106: 739–48.
2. Fawcet K. A., Barroso I. The genetics of obesity: FTO leads
the way. Trends Genet 2010; 26: 266–74.
3. Hubacek J. A., Stanek V., Gebauerová M., Pilipcincová A.,
Dlouhá D., Poledne R. et al. A FTO variant and risk of acute
coronary syndrome. Clin Chim Acta 2010; 411: 1069–72.
4. Kaklamaki V., Yi N., Sadim M., Siziopikou K., Zhang K., Xu
Y. The role of the fat mass and obesity associated gene (FTO)
in breast cancer risk. BMC Med Genet 2011; 13: 52.
Addiction, 107, 1185–1187
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Letters to the Editor
5. Hubacek J. A., Viklicky O., Dlouha D., Bloudickova S.,
Kubinova R., Peasey A. et al. The FTO gene polymorphism is
associated with end-stage renal disease: two large independent case–control studies in a general population. Nephrol
Dial Transplant 2012; 27: 1030–5.
6. Zimmermann E., Kring S. I., Berentzen T. L., Holst C., Pers
T. H., Hansen T. et al. Fatness-associated FTO gene variant
increases mortality independent of fatness in cohorts of
Danish men. PLoS ONE 2009; 4: e4428.
7. Munafò M. R., Flint J. How reliable are scientific studies?
Br J Psychiatry 2010; 197: 257–8.
8. Munafò M. R. Reliability and replicability of genetic association studies. Addiction 2009; 104: 1439–40.
9. Hubacek J. A., Pitha J., Adamkova V., Lanska V., Poledne R.
A common variant in the FTO gene is associated with body
mass index in males and postmenopausal females, but not
in premenopausal females. Czech post-MONICA and 3PMFs
studies. Clin Chem Lab Med 2009; 47: 387–90.
10. Hubáček J. A., Pikhart H., Peasey A., Kubínová R., Bobák M.
FTO variant, energy intake, physical activity and basal
metabolic rate in Caucasians. The HAPIEE study. Physiol
Res 2011; 60: 175–83.
11. Tönjes A., Zeggini E., Kovacs P., Böttcher Y., Schleinitz D.,
Dietrich K. et al. Association of FTO variants with BMI and
fat mass in the self-contained population of Sorbs in
Germany. Eur J Hum Genet 2010; 18: 104–10.
USE OF NICOTINE REPLACEMENT
THERAPY FOR SMOKING REDUCTION
AND TEMPORARY ABSTINENCE: AN
UPDATE OF BEARD ET AL. (2011)
In a recent paper [1], we analysed data from the Smoking
Toolkit Study (http://www.smokinginengland.info)
between February 2007 and June 2009 to assess
whether the use of nicotine replacement therapy (NRT)
to aid smoking reduction (SR) and temporary abstinence
(TA) might undermine or promote complete cessation,
and whether it was associated with meaningful reductions in cigarette consumption. We reported positive associations between the use of NRT for SR and TA and recent
attempts to quit smoking. After adjustment for sociodemographic characteristics and time to first cigarette,
those using NRT for SR smoked 0.6 cigarettes per day
more than those reducing without NRT, while those
using NRT for TA smoked slightly, but not significantly,
more than other smokers. From this, we concluded that
the use of NRT by continuing smokers probably does little
to reduce the harm from smoking, but far from undermining quitting, it may promote it.
However, due to the available sample size, our report
did not separate out the individual and combined ‘effects’
of NRT for SR and for TA. There may be differences
between smokers who use NRT for SR alone, TA alone or
both. The use of multiple harm reduction approaches has
been reported previously to be more effective than the use
of only one approach [2]. The UK’s National Institute for
Addiction © 2012 Society for the Study of Addiction
Health and Clinical Excellence is currently reviewing
NRT use for harm reduction, and this issue has arisen;
it may also arise in other jurisdictions such as the United
States, where extending the licence for NRT may be considered. Now that a sufficient sample size has been accumulated we wish to report a re-analysis and update of
our previous study, using data from the Smoking Toolkit
Study between February 2007 and November 2011.
Smokers (n = 23 137) were classified into those using
NRT for SR alone (6.0%; n = 1391), those using NRT for
TA alone (5.0%; n = 1163), those using NRT for both SR
and TA (7.3%; n = 1683), those attempting SR without
NRT (39.4%; n = 9113) and smokers doing none of these
things (42.3%; n = 9788). Figure 1a shows the mean
daily cigarette consumption according to the five categories listed above, while Fig. 1b shows the percentage
of smokers reporting a quit attempt in the previous 12
months. Differences in cigarette consumption and
attempts to quit smoking among the five groups were
assessed using analysis of variance (ANOVA) and c2
analyses, respectively.
A significant difference was found in cigarette
consumption across the five categories of smoker
(F(2,23051) = 138.347, P = 0.001). The lowest cigarette
consumption was reported among those attempting SR,
followed by those using NRT for SR and TA, those using
NRT for SR, other smokers generally and those using NRT
for TA. A significant difference was also found in attempts
to quit smoking across the five categories of smoker
(c2(4) = 3276.571, P = 0.001). Those using NRT for SR
and TA were the most likely to report a previous quit
attempt, followed by those using NRT for SR, those using
NRT for TA, those attempting SR without NRT and
other smokers generally. Similar findings emerged
following adjustment for confounding variables (i.e.
socio-demographic characteristics and time to first
cigarette of the day).
These new analyses show that there is a need to differentiate between use of NRT for SR and for TA, and that
using NRT for both is associated with a higher propensity
to quit and lower cigarette consumption than is the case
for either alone.
Declarations of interest
E.B. has received conference funding from Pfizer. R.W.
undertakes research and consultancy and receives fees
for speaking from companies that develop and manufacture smoking cessation medications. He also has a share
of a patent for a novel nicotine delivery device.
Acknowledgement
Data collection was funded by the English Department of
Health, Cancer Research UK, Pfizer, Glaxo-SmithKline,
Addiction, 107, 1185–1187
Letters to the Editor
1187
Figure 1 Smoker behaviour as a function of harm reduction activities. (a) Mean cigarette consumption; (b) percentage of smokers reporting
a quit attempt in the previous 12 months. Data are weighted to match the 2001 census. SR: smoking reduction; TA: temporary abstinence;
NRT: nicotine replacement therapy; every category in both graphs differs significantly from every other category: P < 0.001 for all pairwise
comparisons except for the comparison in cigarette consumption between SR with NRT and SR and TA with NRT where P < 0.05; post-hoc
tests were conducted using Scheffé’s method for cigarette consumption and the standardized residual method for the percentage making a
quit attempt. Error bars: 95% confidence intervals
and Johnson and Johnson, who had no involvement in
the design of the study, the analysis or interpretation of
the data, the writing of the report or the decision to
submit the paper for publication. E.B. is funded by a fellowship from the UK Centre for Tobacco Control Studies.
R.W. is funded by Cancer Research UK.
EMMA BEARD & ROBERT WEST
References
1. Beard E., McNeill A., Aveyard P., Fidler J., Michie M., West R.
Use of nicotine replacement therapy for smoking reduction
and during enforced temporary abstinence: a national survey
of English smokers. Addiction 2011; 106: 197–204.
2. Okuyemi K. S., Richter P., Ahluwalia J. S., Mosier M. C., Nazir
N., Resnicow K. Smoking reduction practices among African
American smokers. Nicotine Tob Res 2002; 4: 167–73.
UK Centre for Tobacco Control Studies,
Cancer Research UK Health Behaviour Research Centre,
University College London, WC1E 6BT, UK.
E-mail: e.beard@ucl.ac.uk
Addiction © 2012 Society for the Study of Addiction
Addiction, 107, 1185–1187
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