[Practical Genetic Testing in Gastroenterology]. / Sinnvolle genetische Untersuchungen in der Gastroenterologie.

Genetic testing has become increasingly relevant in daily clinical practice due to the identification of susceptibility genes for several diseases. This article focuses on genetic testing for hereditary pancreatitis, inflammatory bowel disease and fatty liver disease. Several genetic variants that contribute to chronic pancreatitis development have been identified. If the individual aetiology of chronic pancreatitis is unclear, genetic testing for common predisposing variants should be offered. Inflammatory bowel diseases are complex and multifactorial disorders. However, rare mono- or oligogenic forms of disease exist and should be screened for, as personalized therapies can be offered to subsets of these patients. Genetic risk factors also promote the manifestation and progression of fatty liver disease, liver cirrhosis and hepatocellular carcinoma. In conclusion, genetic testing plays an increasing role in delineating the pathogenesis of gastroenterological and hepatic diseases, in the stratification of patients at risk for severe disease complications, and in the optimization of patient care.

Effects of telmisartan and linagliptin when used in combination on blood pressure and oxidative stress in rats with 2-kidney-1-clip hypertension.

OBJECTIVE: To investigate the effects of linagliptin alone and in combination with the angiotensin II receptor blocker (ARB), telmisartan on blood pressure (BP), kidney function, heart morphology and oxidative stress in rats with renovascular hypertension. METHODS: Fifty-seven male Wistar rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2k1c) method]. Animals were randomly divided into four treatment groups (n = 14-18 per group) receiving: telmisartan (10 mg/kg per day in drinking water), linagliptin (89 ppm in chow), combination (linagliptin 89 ppm + telmisartan 10 mg/kg per day) or placebo. An additional group of 12 rats underwent sham surgery. BP was measured one week after surgery. Hypertensive animals entered a 16-week dosing period. BP was measured 2, 4, 8, 12 and 16 weeks after the initiation of treatment. Blood and urine were tested for assessment of kidney function and oxidative stress 6, 10, 14 and 18 weeks after surgery. Blood and urine sampling and organ harvesting were finally performed. RESULTS: Renal stenosis caused an increase in mean ±â€ŠSD systolic BP as compared with the sham group (157.7 ±â€Š29.3 vs. 106.2 ±â€Š20.5 mmHg, respectively; P < 0.001). Telmisartan alone and in combination with linagliptin, normalized SBP (111.1 ±â€Š24.3 mmHg and 100.4 ±â€Š13.9 mmHg, respectively; P < 0.001 vs. placebo). Telmisartan alone and in combination with linagliptin significantly prevented cardiac hypertrophy, measured by heart weight and myocyte diameter. Renal function measured by cystatin C was not affected by 2k1c surgery. Telmisartan significantly increased plasma concentration of cystatin C. 2k1c surgery initiated fibrosis in both kidneys. Telmisartan promoted further fibrotic changes in the clipped kidney, as measured by protein expression of Col1a1 and histology for interstitial fibrosis and glomerulosclerosis. In non-clipped kidneys, telmisartan demonstrated antifibrotic properties, reducing Col1a1 protein expression. Plasma levels of oxidized low-density lipoprotein were higher in the placebo-treated 2k1c rats as compared to sham-operated animals. The increase was abolished by linagliptin alone (P = 0.03 vs. placebo) and in combination with telmisartan (P = 0.02 vs. placebo). Combination therapy also significantly reduced plasma concentration of carbonyl proteins (P = 0.04 vs. placebo). CONCLUSION: Inhibition of type 4 dipeptidyl peptidase with linagliptin did not counter BP-lowering effects of ARB in 2k1c rats. Linagliptin reduced lipid and protein oxidation in 2k1c rats, and this effect was BP-independent.