Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea.
Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea.
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DOI：
10.1016/j.cgh.2012.05.006
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发表时间：
2012-09
影响因子：
12.6
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
--
作者：
Wong, Banny S.;Camilleri, Michael;Carlson, Paula;McKinzie, Sanna;Busciglio, Irene;Bondar, Olga;Dyer, Roy B.;Lamsam, Jesse;Zinsmeister, Alan R.
调节胆汁酸（BA）合成的基因变异与肠易激综合征（IBS）患者的结肠转运有关。我们研究了不同类型IBS患者BA合成和排泄的特点以及遗传特征。在26名健康志愿者、26名肠易激综合征合并便秘患者（IBS- c）和26名肠易激综合征合并腹泻患者（IBS- d）中，我们测量了血清中7α-羟基-4-胆固醇-3-one （C4， BA合成的替代品）和成纤维细胞生长因子（FGF） 19（一种下调BA合成的回肠激素）的水平。对于粪便样本，当参与者被给予高脂肪饮食时，我们测量了BA的浓度、体重和脂肪量。Spearman相关用于探讨各因素之间的关系。我们使用协方差分析分析了各组所有成员中Klotho-β (KLB)的1个多态性和成纤维细胞生长因子受体-4 （FGFR4）的3个多态性。粪便中BA浓度与组间存在相关性（3组比较，P = 0.057）；肠易激- d组高于肠易激- c组（P = 0.017）。IBS-D患者血清C4水平高于IBS-C （P = 0.02）或健康志愿者（P = 0.01）；与健康志愿者相比，38%的IBS-D患者血清C4水平升高。血清C4水平与大便BA浓度（rs = 0.606, P < .001）、血清FGF19 （rs = - 0.324, P = .007）、大便重量（rs = 0.366, P = .003）相关。粪便BA浓度与体重（rs = 0.737, P < 0.001）和脂肪水平（rs = 0.528, P < 0.001）相关。体重指数与血清C4水平（rs = 0.423, P < .001）和粪便BA浓度（rs = 0.507, P < .001）相关，且IBS-D患者体重指数高于其他组（总体P = .036）。FGFR4 rs1966265与粪便BA水平相关（P = 0.032）。与IBS-C患者或健康志愿者相比，IBS-D患者的体重指数更高，BA的合成和排泄水平也更高。血清C4水平可用于鉴别BA吸收不良的IBS-D患者；需要研究来确定一些患者是否有这种疾病的遗传易感性。
Variations in genes that regulate bile acid (BA) synthesis are associated with colonic transit in patients with irritable bowel syndrome (IBS). We investigated features of BA synthesis and excretion and genetic features of patients with different types of IBS. In 26 healthy volunteers, 26 patients with IBS and constipation (IBS-C), and 26 with IBS and diarrhea (IBS-D), we measured serum levels of 7α-hydroxy-4-cholesten-3-one (C4; a surrogate for BA synthesis) and fibroblast growth factor (FGF) 19 (an ileal hormone that downregulates BA synthesis). For stool samples, we measured concentration of BA, weight, and amount of fat when participants were given high-fat diets. Spearman correlations were used to explore relationships among factors. We analyzed 1 polymorphism in Klotho-β (KLB) and 3 in fibroblast growth factor receptor-4 (FGFR4) for all members of each group using analysis of covariance. The concentration of BA in stool was associated with group (for a comparison of 3 groups; P = .057); it was higher in patients with IBS-D than IBS-C (P = .017). The serum level of C4 was higher in patients with IBS-D than IBS-C (P = .02) or healthy volunteers (P = .01); 38% of patients with IBS-D had increased serum levels of C4, compared with healthy volunteers. Serum level of C4 correlated with stool concentration of BA (rs = 0.606; P < .001), serum FGF19 (rs = −0.324; P = .007), and stool weight (rs = 0.366; P = .003). Stool concentration of BA correlated with weight (rs = 0.737; P < .001) and level of fat (rs = 0.528; P < .001). Body mass index correlated with serum level of C4 (rs = 0.423, P < .001) and stool concentration of BA (rs = 0.507, P < .001), and was higher in patients with IBS-D compared with other groups (overall P = .036). FGFR4 rs1966265 was associated with stool level of BA (P = .032). Patients with IBS-D have greater body mass index and synthesize and excrete higher levels of BA than individuals with IBS-C or healthy volunteers. Serum levels of C4 might be used to identify patients with IBS-D who have BA malabsorption; studies are needed to determine if some patients have a genetic predisposition to this disorder.
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影响因子：
29.4
作者：
Rao AS;Wong BS;Camilleri M;Odunsi-Shiyanbade ST;McKinzie S;Ryks M;Burton D;Carlson P;Lamsam J;Singh R;Zinsmeister AR
通讯作者：
Zinsmeister AR
影响因子：
15.9
作者：
Oelkers, P;Kirby, LC;Dawson, PA
通讯作者：
Dawson, PA
DOI：
10.1016/j.cgh.2009.10.020
发表时间：
2010-02
期刊：
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
影响因子：
--
作者：
Odunsi-Shiyanbade ST;Camilleri M;McKinzie S;Burton D;Carlson P;Busciglio IA;Lamsam J;Singh R;Zinsmeister AR
通讯作者：
Zinsmeister AR
DOI：
10.1097/00042737-199602000-00005
发表时间：
1996-02-01
影响因子：
2.1
作者：
Brydon, WG;Nyhlin, H;Merrick, MV
通讯作者：
Merrick, MV
影响因子：
1.9
作者：
Abrahamsson, Hasse;Ostlund-Lindqvist, Ann-Margret;Gillberg, Per-Goran
通讯作者：
Gillberg, Per-Goran