Association of Variations in TPH1 and HTR2B with Gestational Weight Gain and Measures of Obesity

Association of Variations in TPH1 and HTR2B with Gestational Weight Gain and Measures of Obesity
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DOI：
10.1038/oby.2011.253
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发表时间：
2012-01-01
期刊：
OBESITY
影响因子：
6.9
通讯作者：
Park, Kyong Soo
Park, Kyong Soo
中科院分区：
医学2区
文献类型：
--
作者：
Kwak, Soo Heon;Park, Byoung Lae;Park, Kyong Soo

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血清素参与食欲调节和能量稳态。最近，据报道，5-羟色胺受体 2B (Htr2b) 和色氨酸羟化酶 1 (Tph1) 在小鼠妊娠期 β 细胞增殖中起主要作用。我们在 869 名韩国 GDM 女性和精心挑选的 632 名非糖尿病对照受试者中调查了 HTR2B 和 TPH1 与妊娠糖尿病 (GDM) 风险和肥胖指标的遗传关联。根据标记状态，选择 HTR2B 中的 6 个单核苷酸多态性 (SNP) 和 TPH1 中的 10 个 SNP 进行基因分型。 HTR2B 和 TPH1 的基因变异与 GDM 风险无关。在 GDM 女性中，TPH1 的 SNP 与怀孕期间的体重增加显着相关。在非糖尿病对照中，TPH1 的 SNP 与腰围和 BMI 相关。我们还在一项由 8,842 名受试者组成的全基因组关联研究中发现，TPH1 (rs623580) 的一个变体与 BMI 相关。尽管 HTR2B 和 TPH1 的遗传变异与 GDM 风险无关，但我们发现这些变异与肥胖指标显着相关。然而，需要在不同人群中进行进一步的复制研究来证实我们的发现。
Serotonin is involved in appetite regulation and energy homeostasis. Recently, it has been reported that 5-hydroxytryptamine receptor 2B (Htr2b) and tryptophan hydroxylase 1 (Tph1) play major role in beta-cell proliferation in mouse during pregnancy. We investigated the genetic association of HTR2B and TPH1 with risk of gestational diabetes mellitus (GDM) and measures of obesity, in 869 Korean GDM women and carefully selected 632 nondiabetic control subjects. Six single-nucleotide polymorphisms (SNPs) in HTR2B and ten SNPs in TPH1 were selected for genotyping according to their tagging status. Genetic variants in HTR2B and TPH1 were not associated with the risk of GDM. In GDM women, SNPs of TPH1 were significantly associated with weight gain during pregnancy. In nondiabetic controls, SNPs of TPH1 were associated with waist circumference and BMI. We also found that a variant of TPH1 (rs623580) was associated with BMI in a genome-wide association study comprised of 8,842 subjects. Although genetic variants in HTR2B and TPH1 were not associated with risk of GDM, we found significant association of these variants with measures of obesity. However, further replication studies in a different population are required to confirm our findings.