Gonsalkorale W M, Perrey C, Pravica V, Whorwell P J, Hutchinson I V
Department of Medicine, University Hospital of South Manchester, Nell Lane, Manchester M20 2LR, UK.
Gut. 2003 Jan;52(1):91-3. doi: 10.1136/gut.52.1.91.
Inflammation may play a role in the pathogenesis of irritable bowel syndrome in some individuals, such as in those who develop symptoms following a dysenteric illness. Persisting inflammation, resulting from an imbalance of cytokines regulating the inflammatory response, is one possible mechanism. As the elaboration of cytokines is under genetic control, this study was designed to establish whether there might be a genetic predisposition to an altered pattern of anti-inflammatory cytokine production in patients with irritable bowel syndrome.
A total of 230 unselected patients with irritable bowel syndrome and 450 healthy, ethnically matched controls were studied.
DNA was extracted from peripheral blood leucocytes of subjects. Allele and genotype frequencies were determined for the anti-inflammatory cytokine interleukin 10 at the site (-1082) concerned with production in lymphocytes. Transforming growth factor beta(1) (codons 10 and 25) genotypes were also examined in a smaller group of subjects.
Patients with irritable bowel syndrome had significantly reduced frequencies of the high producer genotype for interleukin 10 than controls (21% v 32%; p=0.003). There was no apparent relationship with any particular bowel habit subtype. Genotypes for transforming growth factor beta(1) were not altered.
These preliminary results suggest that at least some patients with irritable bowel syndrome may be genetically predisposed to produce lower amounts of the anti-inflammatory cytokine interleukin 10. This lends some support to the hypothesis that there may be an inflammatory or genetic component in some cases of this condition and that further studies in specific irritable bowel syndrome subgroups are justified.
炎症可能在某些个体的肠易激综合征发病机制中起作用，比如那些在患痢疾性疾病后出现症状的个体。由调节炎症反应的细胞因子失衡导致的持续性炎症是一种可能的机制。由于细胞因子的产生受基因控制，本研究旨在确定肠易激综合征患者是否可能存在抗炎细胞因子产生模式改变的遗传易感性。
共研究了230例未经挑选的肠易激综合征患者以及450名种族匹配的健康对照者。
从研究对象的外周血白细胞中提取DNA。测定淋巴细胞中与抗炎细胞因子白细胞介素10产生相关位点（-1082）的等位基因和基因型频率。还在一小部分研究对象中检测了转化生长因子β1（密码子10和25）的基因型。
肠易激综合征患者白细胞介素10高产生者基因型的频率显著低于对照组（21%对32%；p = 0.003）。与任何特定的肠道习惯亚型均无明显关系。转化生长因子β1的基因型未发生改变。
这些初步结果表明，至少部分肠易激综合征患者可能在遗传上倾向于产生较低量的抗炎细胞因子白细胞介素10。这为该疾病某些病例可能存在炎症或遗传成分这一假说提供了一些支持，并且对特定肠易激综合征亚组进行进一步研究是合理的。
