Wallmeier Dirk, Winkler Julia K, Fleming Thomas, Woehning Annika, Huennemeyer Katharina, Roeder Eva, Nawroth Peter P, Friederich Hans-Christoph, Wolfrum Christian, Schultz Jobst-Hendrik, Rudofsky Gottfried
Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Genes Nutr. 2013 Jun 25;8(6):601-10. doi: 10.1007/s12263-013-0350-x.
The serotonergic pathway plays a major role in the development of obesity. Its activity can be modulated by the 5-HT transporter-linked polymorphic region in the SLC6A4 gene and the upstream variable number of tandem repeats polymorphism in the MAOA gene. We studied whether these genetic modulations have an influence on weight reduction and weight maintenance in a one-year weight reduction program (OPTIFAST52). The polymorphisms were genotyped by PCR in a sample of 135 female and 67 male subjects with severe obesity (44 ± 13 years, 122.3 ± 22.2 kg, BMI: 41.7 ± 6.7 kg/m). The program leads to a total weight loss of 19.9 ± 9.8 kg (16.9 ± 8.3 %) in women and 27.4 ± 13.6 kg (20.4 ± 9.9 %) in men. Anthropometric measurements and blood levels were determined at the start of the program (T0), after the weight reduction phase (T1) and after the subsequent weight maintenance phase at the end of the program (T2). Each polymorphism alone did not significantly influence weight loss or weight maintenance neither in men nor in women. However, women carrying both risk genotypes (SS and 3/3) displayed a lower total weight loss during the program (p = 0.05). This effect derived mainly from difficulties in the weight maintenance phase (p = 0.11), while the weight reduction phase was not affected (p = 0.61). No influence was found in men (p = 0.93). Modulation of the serotonergic pathway by carrying both risk alleles seems to influence success of weight loss programs in women with severe obesity due to problems in stabilizing body weight after weight reduction.
血清素能通路在肥胖症的发生发展中起主要作用。其活性可由SLC6A4基因中与5-羟色胺转运体相关的多态性区域以及MAOA基因中上游串联重复序列可变数目的多态性进行调节。我们研究了在一项为期一年的减重计划（OPTIFAST52）中，这些基因调节是否对体重减轻和体重维持有影响。通过聚合酶链反应（PCR）对135名女性和67名男性严重肥胖受试者（44±13岁，122.3±22.2千克，体重指数：41.7±6.7千克/平方米）的样本进行基因分型。该计划使女性总体重减轻19.9±9.8千克（16.9±8.3%），男性总体重减轻27.4±13.6千克（20.4±9.9%）。在计划开始时（T0）、减重阶段结束后（T1）以及计划结束后的后续体重维持阶段结束时（T2），测定人体测量指标和血液水平。单独的每种多态性对男性和女性的体重减轻或体重维持均无显著影响。然而，携带两种风险基因型（SS和3/3）的女性在该计划期间的总体重减轻较低（p = 0.05）。这种影响主要源于体重维持阶段的困难（p = 0.11），而减重阶段未受影响（p = 0.61）。在男性中未发现影响（p = 0.93）。由于减重后稳定体重存在问题，携带两种风险等位基因对血清素能通路的调节似乎会影响重度肥胖女性减重计划的成功率。
