The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands.
PLoS One. 2012;7(4):e34584. doi: 10.1371/journal.pone.0034584. Epub 2012 Apr 4.
Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics.
This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy.
Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences -0.23 mm (95%CI -0.45 to -0.00) and -0.41 mm (95%CI -0.69 to -0.13), respectively] and a smaller birth length [difference -2.61 mm (95%CI -5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference -33 grams (95%CI -55 to -10)], and tended to be associated with birth weight [difference -38 grams (95%CI -89 to 13)]. This association persisted after adjustment for smoking quantity.
Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene--fetal smoke exposure interactions.
母亲在怀孕期间吸烟与胎儿生长迟缓有关。我们研究了位于 15q25 染色体上（rs1051730）的常见遗传变异是否会改变母亲吸烟与胎儿生长特征的关联，该变异已知与尼古丁代谢有关。
这项研究在 3563 名参与了一项基于人群的前瞻性队列研究的欧洲母亲中进行，该研究从怀孕早期开始。通过邮寄问卷评估吸烟情况，并在每个孕期通过超声检查测量胎儿生长特征。
在怀孕期间不吸烟的母亲（82.9%）中，母亲 rs1051730 与任何胎儿生长特征均无一致关联。在怀孕期间继续吸烟的母亲（17.1%）中，母亲 rs1051730 与头围无关。母亲 rs1051730 的 T 等位基因与第二和第三个孕期胎儿股骨长度较小有关[分别为-0.23 毫米（95%置信区间-0.45 至-0.00）和-0.41 毫米（95%置信区间-0.69 至-0.13）]，且出生长度也较小[差异为-2.61 毫米（95%置信区间-5.32 至 0.11）]。母亲 rs1051730 的 T 等位基因与第三个孕期估计胎儿体重较低有关[差异为-33 克（95%置信区间-55 至-10）]，且与出生体重呈负相关[差异为-38 克（95%置信区间-89 至 13）]。这种关联在调整吸烟量后仍然存在。
我们的结果表明，母亲 rs1051730 基因型改变了母亲怀孕期间吸烟与胎儿长度和体重生长受损的关联。这些结果应被视为假设产生，并表明需要进行大规模全基因组关联研究，重点关注基因与胎儿吸烟暴露的相互作用。
