Schön Sylvia, Prante Christian, Bahr Claudia, Tarnow Lise, Kuhn Joachim, Kleesiek Knut, Götting Christian
Institut für Laboratoriums und Transfusionsmedizin, Herz und Diabeteszentrum Nordrhein-Westfalen, 32545 Bad Oeynhausen, Germany.
Diabetes Care. 2006 Oct;29(10):2295-9. doi: 10.2337/dc06-0344.
Xylosyltransferase I (XT-I) is the chain-initiating enzyme in the biosynthesis of proteoglycans in basement membranes. It catalyzes the transfer of xylose to selected serine residues in the core protein. The XYLT-II gene codes for a protein highly homologous to XT-I. Proteoglycans are important components of basement membranes and are responsible for their permeability properties. Type 1 diabetic patients have an altered proteoglycan metabolism, which results in microvascular complications. Thus, genetic variations in the xylosyltransferase genes might be implicated in the initiation and progression of these complications.
Genotyping of four genetic variations in the genes XYLT-I and XYLT-II was performed in 912 type 1 diabetic patients (453 with and 459 without diabetic nephropathy) using restriction fragment-length polymorphism.
The distribution of the c.343G>T polymorphism in XYLT-I is significantly different between patients with and without diabetic nephropathy (P = 0.03). T-alleles were more frequent in patients with diabetic nephropathy (odds ratio 2.47 [95% CI 1.04-5.83]). The allelic frequencies of the other investigated XYLT-I and XYLT-II variations (XYLT-I: c.1989T>C in exon 9; XYLT-II: IVS6-9T>C and IVS6-14_IVS6-13insG in intron 5; and c.2402C>G: p.T801R in exon 11) were not different between patients with and without diabetic nephropathy.
The XYLT-I c.343G>T polymorphism contributes to the genetic susceptibility to development of diabetic nephropathy in type 1 diabetic patients.
木糖基转移酶I（XT-I）是基底膜蛋白聚糖生物合成中的链起始酶。它催化木糖转移至核心蛋白中特定的丝氨酸残基上。XYLT-II基因编码一种与XT-I高度同源的蛋白质。蛋白聚糖是基底膜的重要组成部分，并决定其通透性。1型糖尿病患者存在蛋白聚糖代谢改变，这会导致微血管并发症。因此，木糖基转移酶基因的遗传变异可能与这些并发症的发生和发展有关。
采用限制性片段长度多态性方法，对912例1型糖尿病患者（453例有糖尿病肾病，459例无糖尿病肾病）的XYLT-I和XYLT-II基因中的四个遗传变异进行基因分型。
XYLT-I基因中c.343G>T多态性在有和无糖尿病肾病的患者中分布存在显著差异（P = 0.03）。T等位基因在糖尿病肾病患者中更常见（优势比2.47 [95%可信区间1.04 - 5.83]）。其他所研究的XYLT-I和XYLT-II变异（XYLT-I：外显子9中的c.1989T>C；XYLT-II：内含子5中的IVS6-9T>C和IVS6-14_IVS6-13insG；以及外显子11中的c.2402C>G：p.T801R）的等位基因频率在有和无糖尿病肾病的患者之间没有差异。
XYLT-I基因的c.343G>T多态性导致1型糖尿病患者发生糖尿病肾病的遗传易感性。
