脊柱裂以及与肌醇、葡萄糖和锌相关的遗传因素。

Spina bifida and genetic factors related to myo-inositol, glucose, and zinc.

作者信息

Groenen P M W, Klootwijk R, Schijvenaars M M V A P, Straatman H, Mariman E C M, Franke B, Steegers-Theunissen R P M

机构信息

Department of Epidemiology and Biostatistics, University Medical Center Nijmegen, Nijmegen, The Netherlands.

出版信息

Mol Genet Metab. 2004 Jun;82(2):154-61. doi: 10.1016/j.ymgme.2004.03.007.

DOI:10.1016/j.ymgme.2004.03.007

PMID:15172003

Abstract

BACKGROUND

Myo-inositol, glucose and zinc and related genetic factors are suggested to be implicated in the etiology of spina bifida. We investigated the biochemical concentrations of these nutrients and polymorphisms in the myo-inositol transporter SLC5A11, myo-inositol synthase ISYNA1, and zinc transporter SLC39A4 in association with spina bifida risk.

METHODS

Seventy-six spina bifida triads only were ascertained. In mothers, fathers, and spina bifida children polymorphisms determined were SLC5A11 (544C > T), ISYNA1 (1029A > G), and SLC39A4 (1069C > T). Serum myo-inositol and glucose, and red blood cell zinc concentrations were determined in mothers and spina bifida children. Transmission disequilibrium tests (TDT) were applied to determine associations between the polymorphisms and spina bifida. Associations between biochemical values and genotypes were studied by one-way analysis of variance (ANOVA). Interactions between alleles, biochemical values, and environmental factors were analyzed by conditional logistic regression.

RESULTS

No association between SLC5A11, ISYNA1, and SLC39A4 and spina bifida was shown, chi2SLC5A11=0.016, P=0.90; chi2SYNA1=1.52, P=0.22; chi2SLC39A4=0.016, P=0.90; and degrees of freedom (df)=1. Maternal glucose concentrations were comparable for the SLC5A11 genotypes. Significantly lower myo-inositol concentrations were observed in mothers with SLC5A11 CC-genotype, mean (SD) 14.2 (2.6)micromol/L compared to SLC5A11 TT-genotype, 17.0 (3.4)micromol/L, P <0.05 . No significant associations were observed between ISYNA1 and myo-inositol and glucose, and between SLC39A4 and zinc. A significant interaction was demonstrated between a maternal glucose < 4.5 mmol/L and ISYNA1 1029A > G polymorphism on spina bifida risk.

CONCLUSION

The combination of maternal glucose < 4.5 mmol/L and ISYNA1 1029A > G polymorphism protects against spina bifida offspring. Moreover, maternal SLC5A11 544C > T polymorphism contributes to the serum myo-inositol concentration. Larger studies should confirm these findings.

摘要

背景

肌醇、葡萄糖、锌及相关遗传因素被认为与脊柱裂的病因有关。我们研究了这些营养素的生化浓度以及肌醇转运体SLC5A11、肌醇合酶ISYNA1和锌转运体SLC39A4中的多态性与脊柱裂风险的关系。

方法

仅确定了76个脊柱裂三联体。在母亲、父亲和脊柱裂患儿中，检测的多态性为SLC5A11（544C>T）、ISYNA1（1029A>G）和SLC39A4（1069C>T）。测定了母亲和脊柱裂患儿的血清肌醇、葡萄糖以及红细胞锌浓度。应用传递不平衡检验（TDT）来确定多态性与脊柱裂之间的关联。通过单因素方差分析（ANOVA）研究生化值与基因型之间的关联。通过条件逻辑回归分析等位基因、生化值和环境因素之间的相互作用。

结果

未显示SLC5A11、ISYNA1和SLC39A4与脊柱裂之间存在关联，SLC5A11的χ2=0.016，P=0.90；ISYNA1的χ2=1.52，P=0.22；SLC39A4的χ2=0.016，P=0.90；自由度（df）=1。SLC5A11基因型的母亲血糖浓度相当。与SLC5A11 TT基因型（17.0[3.4]μmol/L）相比，SLC5A11 CC基因型的母亲肌醇浓度显著降低，平均（标准差）为14.2（2.6）μmol/L，P<0.05。未观察到ISYNA1与肌醇和葡萄糖之间以及SLC39A4与锌之间存在显著关联。母亲血糖<4.5 mmol/L与ISYNA1 1029A>G多态性之间在脊柱裂风险上存在显著相互作用。