Kim Jae-Min, Stewart Robert, Kim Sung-Wan, Yang Su-Jin, Shin Il-Seon, Yoon Jin-Sang
Department of Psychiatry and Depression Clinical Research Center, Chonnam National University Medical School, Kwangju, Republic of Korea.
Psychosom Med. 2009 Apr;71(3):286-91. doi: 10.1097/PSY.0b013e3181990fff. Epub 2009 Feb 27.
To investigate the modifying effects of two candidate genes (serotonin transporter gene linked promoter region (5-HTTLPR) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms) on the associations between general somatic morbidity and incidence of depression in an East Asian population with high frequencies of potential risk alleles.
With a 2-year prospective study of a community sample (N = 521) of older people (aged 65+), information on baseline number of health complaints, diagnosis of moderate/severe depressive syndrome (Geriatric Mental State), and genotypes for 5-HTTLPR and MTHFR C677T polymorphisms were ascertained. Interactions between somatic morbidity and the two genotypes were investigated for incident depression.
Incident depression was present in 63 (12%) and was associated with worse somatic health. Significant interactions between number of somatic complaints and both genotypes were observed. For the 5-HTTLPR genotypes, the association between the number of somatic disorders and depression was significant in s/s homozygotes (chi2 = 8.80 (1 df), p = .003) but not in heterozygotes (chi2 = 0.23, p = .634) or l/l homozygotes (chi2 = 0.04, p = .840). For the MTHFR genotypes, the association between the number of somatic disorders and depression was significant in T/T homozygotes (chi2 = 4.97, p = .026) but not in C/T heterozygotes (chi2 = 1.24, p = .265) or C/C homozygotes (chi2 = 1.04, p = .307).
These findings suggest that associations between general somatic morbidity and late-life depression are modified by at least two genes, and that elders with particular genotypes are at greater risk for onset of depression in the presence of somatic ill health.
在具有高频率潜在风险等位基因的东亚人群中，研究两个候选基因（血清素转运体基因连锁启动子区域（5-HTTLPR）和亚甲基四氢叶酸还原酶（MTHFR）C677T多态性）对一般躯体疾病与抑郁症发病率之间关联的修饰作用。
对一个社区样本（N = 521）的老年人（年龄65岁及以上）进行为期2年的前瞻性研究，确定了关于基线健康问题数量、中度/重度抑郁综合征诊断（老年精神状态）以及5-HTTLPR和MTHFR C677T多态性的基因型信息。研究躯体疾病与这两种基因型之间的相互作用对新发抑郁症的影响。
63人（12%）出现新发抑郁症，且与较差的躯体健康状况相关。观察到躯体问题数量与两种基因型之间存在显著的相互作用。对于5-HTTLPR基因型，躯体疾病数量与抑郁症之间的关联在s/s纯合子中显著（χ2 = 8.80（1自由度），p = 0.003），但在杂合子中不显著（χ2 = 0.23，p = 0.634）或l/l纯合子中不显著（χ2 = 0.04，p = 0.840）。对于MTHFR基因型，躯体疾病数量与抑郁症之间的关联在T/T纯合子中显著（χ2 = 4.97，p = 0.026），但在C/T杂合子中不显著（χ2 = 1.24，p = 0.265）或C/C纯合子中不显著（χ2 = 1.04，p = 0.307）。
这些发现表明，一般躯体疾病与晚年抑郁症之间的关联至少受到两个基因的修饰，并且具有特定基因型的老年人在存在躯体健康问题时患抑郁症的风险更高。
