Mottes Monica, Belpinati Francesca, Milani Monia, Saccomandi Daniela, Petrelli Elena, Calacoci Marisa, Chierici Roberta, Pignatti Pier Franco, Borgna-Pignatti Caterina
Department of Mother and Child, Biology and Genetics, University of Verona, Verona, Italy.
Clin Chem Lab Med. 2008;46(7):980-4. doi: 10.1515/CCLM.2008.189.
Adult-type hypolactasia is characterized by the inability to digest lactose during adulthood, due to lactase (LCT) deficiency. It is usually diagnosed by the measurement of breath hydrogen increase after a lactose load (breath hydrogen test, BHT). A substitution of C to T at position -13910 bp upstream the LCT gene (rs4988235), in a regulatory region, was found to be strongly associated with the lactase persistence phenotype in North-European populations.
We investigated the -13910 C/T polymorphism to determine LCT genotype distribution and to validate genetic testing for adult-type hypolactasia in a Southern European population. A total of 43 children referred for suspected lactose malabsorption were enrolled in the study, their parents and siblings (whole sample=112 individuals) also took the breath test, and all were enrolled for clinical monitoring and genotype determination. In addition, 125 unrelated blood donors from the same geographic area were genotyped for the calculation of allelic frequencies. The frequency of C/C genotypes was 70%.
The correlation between the C/C genotype (which should correspond to lactose non-digesters) and positive BHT in unrelated family founders was significant (chi(2)=16.7, p<0.002). The genetic test compared to the BHT had a sensitivity of 95% and 91% and a specificity of 48% and 55% in adults and children, respectively.
Low specificity might be due to intrinsic limitations of the standard BHT or to other possible mutations, although no sequence variation was found upon sequencing a 253 bp fragment of the LCT regulatory region in asymptomatic individuals.
成人型低乳糖酶症的特征是成年后由于乳糖酶（LCT）缺乏而无法消化乳糖。通常通过测量乳糖负荷后呼出氢气的增加量（呼气氢试验，BHT）来进行诊断。在LCT基因上游-13910 bp位置（rs4988235）的一个调控区域中，C到T的替换被发现与北欧人群中的乳糖酶持续存在表型密切相关。
我们研究了-13910 C/T多态性，以确定LCT基因型分布，并在南欧人群中验证成人型低乳糖酶症的基因检测。共有43名因疑似乳糖吸收不良而转诊的儿童参加了该研究，他们的父母和兄弟姐妹（整个样本=112人）也进行了呼气试验，所有人都参加了临床监测和基因型测定。此外，对来自同一地理区域的125名无关献血者进行基因分型以计算等位基因频率。C/C基因型的频率为70%。
在无关的家族创始人中，C/C基因型（应对应乳糖不消化者）与阳性BHT之间的相关性显著（χ²=16.7，p<0.002）。与BHT相比，基因检测在成人和儿童中的敏感性分别为95%和91%，特异性分别为48%和55%。
低特异性可能是由于标准BHT的内在局限性或其他可能的突变，尽管在对无症状个体的LCT调控区域的253 bp片段进行测序时未发现序列变异。
