Department of Clinical Sciences, Lund University, Clinical Research Center, Entrance 72, Building 91, Floor 12, Malmö University Hospital, Malmö SE 205 02, Sweden.
Heart. 2013 Jul;99(13):949-53. doi: 10.1136/heartjnl-2013-303634. Epub 2013 Apr 27.
The brain derived neurotrophic factor (BDNF) locus has been implicated in psychiatric and substance related disorders. Recent genome-wide association studies (GWAS) have shown strong associations between single nucleotide polymorphisms in BDNF, smoking behaviour and high body mass index (BMI). Our aim was to test whether genetic BDNF variation alters the risk of smoking related morbidity and mortality.
Cox proportional hazards models were used to relate the BDNF rs4923461(A/G) polymorphisms to all-cause, cancer and cardiovascular mortality and cardiovascular disease (CVD) incidence adjusted for age, sex, BMI, and smoking quantity.
The Malmö Diet and Cancer Study (MDCS), a population based prospective cohort study (n=30 447).
We obtained complete data on 25 071 subjects, of whom 6507 were current smokers and 18 564 were non-smokers who underwent a baseline examination from 1991-1996.
During a mean follow-up time of 12 years, 1049 deaths (346 cardiovascular deaths and 492 cancer deaths) and 802 incident CVD events occurred among current smokers.
The major allele (A) of rs4923461 was significantly associated with ever having smoked (p=0.03) and high BMI (p=0.001). The A-allele was associated with risk of all-cause (HR=1.12, 95% CI 1.00 to 1.25; p<0.05) and CVD (HR=1.23, 95% CI 1.01 to 1.49; p=0.04) mortality. There was no significant association between the rs4923461 and cancer mortality or CVD incidence.
Our data suggest that smoking- and obesity-associated variation of the BDNF gene affects the risk of death, especially due to cardiovascular causes, in smokers. Determination of the BDNF genotype in smokers may guide the need for smoking cessation interventions.
脑源性神经营养因子（BDNF）基因座与精神和物质相关障碍有关。最近的全基因组关联研究（GWAS）表明，BDNF 单核苷酸多态性与吸烟行为和高体重指数（BMI）之间存在强烈关联。我们的目的是测试遗传 BDNF 变异是否会改变与吸烟相关的发病率和死亡率的风险。
使用 Cox 比例风险模型将 BDNF rs4923461(A/G)多态性与全因、癌症和心血管死亡率以及心血管疾病（CVD）发生率相关联，这些因素经过年龄、性别、BMI 和吸烟量调整。
马尔默饮食与癌症研究（MDCS），一项基于人群的前瞻性队列研究（n=30447）。
我们获得了 25071 名受试者的完整数据，其中 6507 名是当前吸烟者，18564 名是在 1991-1996 年进行基线检查的非吸烟者。
在平均 12 年的随访期间，当前吸烟者中有 1049 人死亡（346 例心血管死亡和 492 例癌症死亡）和 802 例新发 CVD 事件。
rs4923461 的主要等位基因（A）与曾经吸烟（p=0.03）和高 BMI（p=0.001）显著相关。A 等位基因与全因（HR=1.12，95%CI 1.00 至 1.25；p<0.05）和 CVD（HR=1.23，95%CI 1.01 至 1.49；p=0.04）死亡率相关。rs4923461 与癌症死亡率或 CVD 发病率之间没有显著关联。
我们的数据表明，BDNF 基因与吸烟和肥胖相关的变异会影响吸烟者的死亡风险，特别是由于心血管原因。在吸烟者中确定 BDNF 基因型可能有助于确定是否需要进行戒烟干预。
