Do genetic variants in the SPINK1 gene affect the level of serum PSTI?
Do genetic variants in the SPINK1 gene affect the level of serum PSTI?
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DOI：
10.1007/s00535-012-0590-3
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发表时间：
2012-11-01
影响因子：
6.3
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
--
作者：
Kume, Kiyoshi;Masamune, Atsushi;Shimosegawa, Tooru
丝氨酸蛋白酶抑制剂Kazal 1型（SPINK1），也称为胰腺分泌性胰蛋白酶抑制剂（PSTI），是一种由胰腺腺泡细胞分泌的肽。遗传学研究表明 SPINK1 基因变异与慢性胰腺炎或复发性急性胰腺炎之间存在关联。本研究的目的是阐明SPINK1变异是否影响血清PSTI水平。招募了163名慢性胰腺炎或复发性急性胰腺炎患者和73名健康对照者。使用商业放射免疫测定试剂盒测定血清 PSTI 浓度。鉴定出 10 名患者具有 p.N34S 变异，7 名患者具有 IVS3+2T > C 变异，2 名患者同时具有 p.N34S 和 IVS3+2T > C 变异，以及 1 名患者具有 SPINK1 基因中新型错义 p.P45S 变异。无 SPINK1 变异的患者的血清 PSTI 水平为 14.3 +/- A 9.6 ng/ml（平均值 +/- A SD），健康对照者的血清 PSTI 水平为 10.7 +/- A 2.2 ng/ml。携带 IVS3+2T > C 变异的患者 (5.1 +/- A 3.4 ng/ml)，但携带 p.N34S 变异的患者 (8.9 +/- A 3.5 ng/ml)，其 PSTI 水平显着低于无 SPINK1 变异的患者和健康对照。 p.P45S 变异患者的血清 PSTI 水平为 4.9 ng/ml。低水平的血清 PSTI (< 6.0 ng/ml) 在区分 IVS3+2T > C 和 p.P45S 携带者与非携带者方面的敏感性为 80%，特异性为 97%，准确度为 96%。 SPINK1 基因 IVS3+2T > C 和 p.P45S 变体患者的血清 PSTI 水平降低。
The serine protease inhibitor Kazal type 1 (SPINK1), also known as pancreatic secretory trypsin inhibitor (PSTI), is a peptide secreted by pancreatic acinar cells. Genetic studies have shown an association between SPINK1 gene variants and chronic pancreatitis or recurrent acute pancreatitis. The aim of this study was to clarify whether the SPINK1 variants affect the level of serum PSTI.One hundred sixty-three patients with chronic pancreatitis or recurrent acute pancreatitis and 73 healthy controls were recruited. Serum PSTI concentrations were determined with a commercial radioimmunoassay kit.Ten patients with the p.N34S variant, 7 with the IVS3+2T > C variant, two with both the p.N34S and the IVS3+2T > C variants, and one with the novel missense p.P45S variant in the SPINK1 gene were identified. The serum PSTI level in patients with no SPINK1 variants was 14.3 +/- A 9.6 ng/ml (mean +/- A SD), and that in healthy controls was 10.7 +/- A 2.2 ng/ml. The PSTI level in patients carrying the IVS3+2T > C variant (5.1 +/- A 3.4 ng/ml), but not in those with the p.N34S variant (8.9 +/- A 3.5 ng/ml), was significantly lower than that in the patients without the SPINK1 variants and the healthy controls. The serum PSTI level in the patient with the p.P45S variant was 4.9 ng/ml. Low levels of serum PSTI (< 6.0 ng/ml) showed sensitivity of 80 %, specificity of 97 %, and accuracy of 96 % in the differentiation of IVS3+2T > C and p.P45S carriers from non-carriers.Serum PSTI levels were decreased in patients with the IVS3+2T > C and p.P45S variants of the SPINK1 gene.