Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Switzerland.
Pharmacogenet Genomics. 2011 Sep;21(9):559-64. doi: 10.1097/FPC.0b013e328348f70c.
Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative colitis (UC), are multifactorial disorders, characterized by chronic inflammation of the intestine. A number of genetic components have been proposed to contribute to IBD pathogenesis. In this case-control study, we investigated the association between two common vitamin D-binding protein (DBP) genetic variants and IBD susceptibility. These two single nucleotide polymorphisms (SNPs) in exon 11 of the DBP gene, at codons 416 (GAT>GAG; Asp>Glu) and 420 (ACG>AAG; Thr>Lys), have been previously suggested to play roles in the etiology of other autoimmune diseases.
Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants.
On statistical analysis, we observed that the DBP 420 variant Lys is less frequent in IBD cases than in non-IBD controls (allele frequencies, P=0.034; homozygous carrier genotype frequencies, P=0.006). This inverse association between the DBP 420 Lys and the disease remained significant, when non-IBD participants were compared with UC (homozygous carrier genotype frequencies, P=0.022) or Crohn's disease (homozygous carrier genotype frequencies, P=0.016) patients separately. Although the DBP position 416 alone was not found to be significantly associated with IBD, the haplotype DBP_2, consisting of 416 Asp and 420 Lys, was more frequent in the non-IBD population, particularly notably when compared with the UC group (Odds ratio, 4.390).
Our study adds DBP to the list of potential genes that contribute to the complex genetic etiology of IBD, and further emphasizes the association between vitamin D homeostasis and intestinal inflammation.
炎症性肠病（IBD）、克罗恩病和溃疡性结肠炎（UC）是多种因素导致的疾病，其特征为肠道慢性炎症。许多遗传因素被认为与 IBD 的发病机制有关。在本病例对照研究中，我们研究了两个常见的维生素 D 结合蛋白（DBP）基因遗传变异与 IBD 易感性之间的关系。这两个单核苷酸多态性（SNP）位于 DBP 基因外显子 11 上的密码子 416（GAT>GAG；天冬氨酸>谷氨酸）和 420（ACG>AAG；苏氨酸>赖氨酸），先前被认为在其他自身免疫性疾病的发病机制中起作用。
我们使用 TaqMan SNP 技术对 884 名个体（636 名 IBD 病例和 248 名非 IBD 对照）的两个 DBP 变体进行了基因分型。
在统计分析中，我们观察到 DBP 420 变体 Lys 在 IBD 病例中的频率低于非 IBD 对照组（等位基因频率，P=0.034；纯合子携带者基因型频率，P=0.006）。当将非 IBD 参与者与 UC（纯合子携带者基因型频率，P=0.022）或克罗恩病（纯合子携带者基因型频率，P=0.016）患者分别进行比较时，这种 DBP 420 Lys 与疾病之间的反向关联仍然显著。尽管 DBP 位置 416 本身与 IBD 无显著关联，但包含 416 位天冬氨酸和 420 位赖氨酸的 DBP_2 单倍型在非 IBD 人群中更为常见，尤其是与 UC 组相比（比值比，4.390）。
本研究将 DBP 添加到潜在基因列表中，这些基因有助于 IBD 的复杂遗传病因，并进一步强调了维生素 D 稳态与肠道炎症之间的关联。
