Shaw G M, Wasserman C R, Murray J C, Lammer E J
March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Emeryville, California 94608, USA.
Cleft Palate Craniofac J. 1998 Jul;35(4):366-70. doi: 10.1597/1545-1569_1998_035_0366_itagoc_2.3.co_2.
We previously demonstrated a strong association between periconceptional maternal cigarette smoking, infant transforming growth factor-alpha (TGFa) genotype, and risk of orofacial clefts. Because serum folate may be decreased by cigarette smoking and because maternal periconceptional use of multivitamins containing folic acid has been associated with a reduced risk of clefting, we explored whether a potential relation existed between infant TGFa genotype, maternal multivitamin use, and risk of orofacial cleft phenotypes.
Data were derived from a population-based case-control study of fetuses and live-born infants among a cohort of 1987 to 1989 California births (n = 548,844). Information concerning periconceptional multivitamin use was obtained via telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants, and of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening bloodspots and genotyped for the Taql polymorphism of TGFa. Among infants of interviewed mothers, genotypes were available for 571 (78.1%) case infants and 640 (87.2%) control infants.
The study encompassed all hospitals in selected California counties.
The main outcome measures were the risks of specific cleft phenotypes among infants with uncommon TGFa genotypes and whose mothers did not use multivitamins periconceptionally.
Compared with infants homozygous for the common TGFa genotype and whose mothers used multivitamins, increased clefting risks were observed for infants with the A2 genotype (homozygous or heterozygous) and whose mothers did not use multivitamins. Risk estimates were 3.0 (1.4-6.6 [95% confidence interval]) for isolated cleft lip with or without cleft palate (CLP), 2.4 (0.69-11.6) for multiple CLP, 2.6 (0.97-7.7) for isolated cleft palate (CP), 4.2 (1.3-16.2) for multiple CP, and 8.1 (2.6-27.7) for "known-syndrome" clefts. Clefting risks for infants with the A2 genotype and whose mothers used multivitamins were substantially smaller, as were the risks for infants with the A1 genotype whose mothers did not use multivitamins.
These data provide preliminary evidence for a gene-nutrient interaction in risk of clefting.
我们之前已证明孕期母亲吸烟、婴儿转化生长因子α（TGFα）基因型与口面部裂隙风险之间存在紧密关联。由于吸烟可能会降低血清叶酸水平，且孕期母亲使用含叶酸的多种维生素与降低裂隙风险相关，因此我们探究了婴儿TGFα基因型、母亲使用多种维生素与口面部裂隙表型风险之间是否存在潜在关联。
数据源自一项基于人群的病例对照研究，研究对象为1987年至1989年加利福尼亚州出生队列中的胎儿和活产婴儿（n = 548,844）。通过电话访谈731名（符合条件的84.7%）口面部裂隙病例婴儿的母亲和734名（78.2%）非畸形对照婴儿的母亲，获取有关孕期使用多种维生素的信息。从新生儿筛查血斑中获取DNA，并对TGFα的TaqI多态性进行基因分型。在接受访谈母亲的婴儿中，571名（78.1%）病例婴儿和640名（87.2%）对照婴儿有可用的基因型。
该研究涵盖加利福尼亚州选定县的所有医院。
主要观察指标为TGFα基因型罕见且母亲孕期未使用多种维生素的婴儿中特定裂隙表型的风险。
与TGFα基因型常见且母亲使用多种维生素的婴儿相比，A2基因型（纯合子或杂合子）且母亲未使用多种维生素的婴儿，其裂隙风险增加。孤立性唇裂伴或不伴腭裂（CLP）的风险估计值为3.0（1.4 - 6.6[95%置信区间]），多发性CLP为2.4（0.69 - 11.6），孤立性腭裂（CP）为2.6（0.97 - 7.7），多发性CP为4.2（1.3 - 16.2），“已知综合征”性裂隙为8.1（2.6 - 27.7）。A2基因型且母亲使用多种维生素的婴儿的裂隙风险显著较小，母亲未使用多种维生素的A1基因型婴儿的风险也较小。
这些数据为裂隙风险中的基因 - 营养素相互作用提供了初步证据。
