Association of distinct α2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders
Association of distinct α2 adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders
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DOI：
10.1136/gut.2003.030882
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发表时间：
2004-06-01
期刊：
影响因子：
24.5
通讯作者：
Urrutia, R
中科院分区：
文献类型：
--
作者：
Kim, HJ;Camilleri, M;Urrutia, R
背景：遗传学在肠易激综合征（IBS）表型表现中的作用尚不清楚。我们的目的是：(1)比较低功能胃肠疾病（FGID）患者和健康对照者中α 2 （α(2)）肾上腺素受体、去甲肾上腺素转运蛋白和血清素转运蛋白（可溶性载体蛋白成员4 (SLC6A4)）启动子多态性的患病率；(2)测试这些遗传变异与肠易激综合征症状和高躯体症状评分之间的关联。方法：经过验证的肠道和躯体症状问卷描述了表型：90例IBS便秘（IBS- c）， 128例IBS腹泻，38例IBS交替肠功能，20例慢性腹痛。Logistic回归分析评估了α(2)肾上腺素能受体和SLC6A4不同多态性与IBS或慢性腹痛表型和高躯体评分的相关性。结果：两种不同的多态性独立地与IBS-C表型相关：α (2C) Del 322-325(优势比（OR） 2.48(95%可信区间（CI） 0.98, 6.28)；p = 0.05)和α (2A)-1291 (C- >G) (OR 1.66 (95% CI 0.94, 2.92)；P = 0.08)。总体而言，α (2C) Del 322-325多态性（单独或联合其他多态性）也与高躯体症状评分显著相关(or 2.2 (95% CI 1.06, 4.64)；P = 0.03)。多态性组合也与高体细胞得分相关。结论：功能上不同的α (2A)和α (2C)肾上腺素能受体和血清素转运体多态性与低功能胃肠道疾病患者的便秘和高度躯体症状有关，尽管遗传对表型的贡献强度尚不清楚。
Background: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (alpha(2)) adrenoceptors, norepinephrine transporter, and serotonin transporter protein ( soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and high somatic symptom scores.Methods: Validated bowel and somatic symptom questionnaires characterised the phenotype: 90 with IBS constipation (IBS-C), 128 IBS diarrhoea, 38 IBS alternating bowel function, and 20 chronic abdominal pain. Logistic regression analyses assessed associations of different polymorphisms for alpha(2) adrenoceptor and SLC6A4 with IBS or chronic abdominal pain phenotypes and high somatic score.Results: Two distinct polymorphisms independently appeared to be associated with the phenotype IBS-C: alpha(2C) Del 322-325 (odds ratio (OR) 2.48 (95% confidence interval (CI) 0.98, 6.28); p = 0.05) and alpha(2A)-1291 (C-->G) (OR 1.66 (95% CI 0.94, 2.92); p = 0.08) relative to wild-type. Overall, the alpha(2C) Del 322-325 polymorphism (alone or combined with other polymorphisms) was also significantly associated with a high somatic symptom score (OR 2.2 (95% CI 1.06, 4.64); p = 0.03). Combinations of polymorphisms were also associated with high somatic scores.Conclusion: Functionally distinct alpha(2A) and alpha(2C) adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear.