Byrne J, Cama A, Vigliarolo M, Levato L
Boyne Research Institute, Droghedo, Ireland.
Ir Med J. 1997 Jan-Feb;90(1):32-4.
Neural tube defects (NTDs) may result from a genetic susceptibility interacting with environmental exposures occurring early in pregnancy. Current research is concerned with enlarging our understanding of the action of folic acid, a B group vitamin, which has been shown to prevent the occurrence of NTDs in clinical trials. Despite the epidemic waves in the incidence of NTDs and the existence of areas with very high rates, there have been few studies that explored the genetic contribution to NTDs in high rates versus low rate areas. We investigated the genetic epidemiologic factors that occur in NTD families and compared their frequency in a high rate area-Ireland-with a low rate area-Italy. We explored the existence of three features indicative of hereditary factors and found that all three factors were higher in Ireland than in Italy. These factors were (i) sibling recurrence risk (3.3% vs 1.6%; p = 0.2), (ii), other malformations in siblings (11.5% vs 3.3%; p < 0.001) and (iii) average number of children in mothers' families vs fathers' families (average difference in Ireland 1.0 vs 0.4 in Italy; p < 0.1). These results support the motion that geographic differences in occurrence of NTDs are due at least in part to differing prevalences of genetic susceptibility factors. Further epidemiological and molecular studies are needed to confirm this observation. In addition, studies of the interactions between environmental agents and genetic susceptibility will be important in determining their relative contributions.
神经管缺陷（NTDs）可能源于遗传易感性与孕期早期发生的环境暴露之间的相互作用。当前的研究致力于加深我们对叶酸（一种B族维生素）作用的理解，叶酸在临床试验中已被证明可预防NTDs的发生。尽管NTDs的发病率存在流行波动，且存在发病率极高的地区，但很少有研究探讨高发病率地区与低发病率地区NTDs的遗传贡献。我们调查了NTD家庭中出现的遗传流行病学因素，并比较了其在高发病率地区——爱尔兰——和低发病率地区——意大利——的频率。我们探究了表明遗传因素的三个特征的存在情况，发现这三个因素在爱尔兰均高于意大利。这些因素分别为：（i）同胞复发风险（3.3%对1.6%；p = 0.2），（ii）同胞中的其他畸形（11.5%对3.3%；p < 0.001），以及（iii）母亲家族与父亲家族的子女平均数量（爱尔兰的平均差异为1.0，而意大利为0.4；p < 0.1）。这些结果支持了这样一种观点，即NTDs发生率的地理差异至少部分归因于遗传易感性因素的不同患病率。需要进一步的流行病学和分子研究来证实这一观察结果。此外，研究环境因素与遗传易感性之间的相互作用对于确定它们的相对贡献将是重要的。
