Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients

AIM:To investigate the interaction of interleukin-23 receptor(IL23R)(rs1004819 and rs2201841),autophagy-related 16-like 1(ATG16L1)(rs2241880), caspase recruitment domain-containing protein 15 (CARD15)genes,and IBD5 locus in Crohn's disease(CD) patients. METHODS:A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped.Interactions and specific genotype combinations of a total of eight variants were tested.The variants of IBD5locus(IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868),CARD15(R702W rs2066845 and L1007fs rs2066847),ATG16L1(rs2241880)and IL23R (rs1004819,rs2201841)genes were genotyped by PCR-RFLP,the G908R(rs2066844)in CARD15 was determined by direct sequencing. RESULTS:The association of ATG16L1 T300A with CD was confirmed[P=0.004,odds ratio(OR)=1.69, 95%CI:1.19-2.41],and both IL23R variants were found to represent significant risk for the disease(P= 0.008,OR=2.05,95%CI:1.20-3.50 for rs1004819 AA;P<0.001,OR=2.97,95%CI:1.65-5.33 for rs2201841 CC).Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD)loci indicated that IL23R,ATG16L1,CARD15 and IBD5(IGR2198a_1)contribute independently to disease risk.We also analysed the specific combina- tions by pair of individual ATG16L1,IL23R rs1004819, rs2201841,IGR2198a_1,IGR2096a_1 and CARD15 genotypes for disease risk influence.In almost all cases,the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism.The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status(P<0.001,OR=9.15,95% CI:2.05-40.74). CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.

Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet

AIM: To determine the fasting plasma carnitine ester in patients with celiac disease.METHODS: We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet.RESULIS: The level of free camitine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced (4.703 ± 0.205 vs 10.227 ± 0.368 nmol/mL,P＜0.01). The level of propionylcarnitine was 61.5%,butyrylcarnitine 56.9%, hexanoylcarnitine 75%,octanoylcarnitine 71.1%, octenoylcarnitine 52.1%,decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%,lauroylcarnitine 61.5%, miristoylcarnitine 66.7%,miristoleylcarnitine 62.5% and oleylcarnitine 81.1%in the celiac disease patients compared to the control values, respectively (P＜0.01).CONCLUSION: The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.

No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

瞄准：当前的工作的目标细胞毒素的 T 淋巴细胞抗原是分析 +49A/G 的流行变体的在有 Crohn 的匈牙利病人的 4 基因(CTLA4 )?&#713;s 疾病(CD ) 和 ulcerative (UC ) 。方法：有 CD 的 130 个无关的题目的一个总数并且 150 与 UC，和 170 匹配的控制是为单个核苷酸多型性(SNP ) 的 genotyped。遗传型被使用 PCR/RFLP 测试决定。结果：G 等位基因频率和 GG 遗传型的流行在 CD 组，是 38.1% 和 12.3%40.6% 和 18.6% 在 UC 病人，并且 37.4% 和 15.9% 在控制组分别地。结论：当前的学习的结果显示出 +49G SNP 的那辆马车在异质接合或不在匈牙利人口为 CD 或为 UC 在同型结合的形式授与风险任何一个。

IL23R single nucleotide polymorphisms could be either beneficial or harmful in ulcerative colitis

AIM To investigate the association of seven single nucleotide polymorphisms(SNPs) of the IL23 R gene with the clinical picture of ulcerative colitis(UC). METHODS Genomic DNA samples of 131 patients (66 males, 65 females, mean age 55.4 ± 15.8 years) with Caucasian origin, diagnosed with UC were investigated. The diagnosis of UC was based on the established clinical, endoscopic, radiological, and histopathological guidelines. DNA was extracted from peripheral blood leukocytes by routine salting out method. Polymerase chain reaction and restriction fragment length polymorphism were used to identify the alleles of seven SNPs of IL23 R gene(rs11209026, rs10889677, rs1004819, rs2201841, rs7517847, rs10489629, rs7530511).RESULTS Four out of seven analyzed SNPs had statistically significant influence on the clinical picture of UC. Two SNPs were associated with greater colonic extension(rs2201841 P = 0.0084; rs10489629 P = 0.0405). For two of the SNPs, there was more frequently need for operations (rs2201841 P = 0.0348, OR = 8.0; rs10889677 P = 0.0347, OR = 8.0). The rs2201841 showed to be a risk factor for the development of iron deficiency (P = 0.0388, OR = 6.1837). For patients with the rs10889677, a therapy with azathioprine was more frequently necessary(P = 0.0116, OR = 6.1707). Patients with rs10489629 SNP had a lower risk for weight loss(P = 0.0169, OR = 0.3394). Carriers of the heterozygous variant had a higher risk for an extended disease (P = 0.0284). The rs7517847 showed a protective character leading to mild bowel movements. Three SNPs demonstrated no statistically significant influence on any examined clinical features of UC.CONCLUSION We demonstrated susceptible or protective character of the investigated IL23 R SNPs on the phenotype of UC, confirming the genetic association.

Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis

瞄准：与溃疡的 culitis (UC ) 并且与健康控制题目相比在成年病人决定血浆肉毒碱酉旨侧面。方法：用 ESI 三倍的四极双人脚踏车团分光术，肉毒碱酉旨侧面与 UC 和 44 匹配年龄、匹配性的健康控制在 44 个病人被测量。结果：在免费肉毒碱与 UC 和健康控制在病人之间铺平的 fasting 没有有效差量。禁食 propionyl-(0.331 +/- 0.019 对 0.392 +/- 0.017 micromol/L ) ， butyryl-(0.219 +/- 0.014 对 0.265 +/- 0.012 ) ，并且 isovalerylcarnitine (0.111 +/- 0.008 对 0.134 +/- 0.008 ) 层次在 UC 病人被减少。由对比，octanoyl-的水平( 0.147 +/- 0.009 对 0.114 +/- 0.008 )，decanoyl-( 0.180 +/- 0.012 对 0.137 +/- 0.008 )，myristoyl-( 0.048 +/- 0.003 对 0.039 +/- 0.003 )，palmitoyl-( 0.128 +/- 0.006 对 0.109 +/- 0.004 )，palmitoleyl-( 0.042 +/- 0.003 对 0.031 +/- 0.002 )并且 oleylcarnitine ( 0.183 +/- 0.007 对 0.163 +/- 0.007 ；P 【 0.05 在所有比较) 与 UC 在病人被增加。结论：我们的数据在 UC 病人建议肉毒碱酉旨的选择参与，可能由于他们的改变的新陈代谢。

Prevalence of SLC22A4, SLC22A5 and CARD15 gene mutations in Hungarian pediatric patients with Crohn’s disease

AIM: To investigate the frequency of the common NOD2/CARD15 susceptibility variants and two functional polymorphisms of OCTN cation transporter genes in Hungarian pediatric patients with Crohn’s disease (CD). METHODS: A cohort of 19 unrelated pediatric and 55 unrelated adult patients with Crohn’s disease and 49 healthy controls were studied. Genotyping of the three common CD-associated CARD15 variants (Arg702Trp, Gly908Arg and 1007finsC changes) with the SLC22A4 1672C→T, and SLC22A5 -207G→C mutations was performed by direct sequencing of the specifi c regions of these genes.RESULTS: At least one CARD15 mutation was present in 52.6% of the children and in 34.5% of the adults compared to 14.3% in controls. Surprisingly, strongly different mutation profi le was detected in the pediatric versus adult patients. While the G908R and 1007finsC variants were 18.4% and 21.1% in the pediatric group, they were 1.82% and 11.8% in the adults, and were 1.02% and 3.06% in the controls, respectively. The R702W allele was increased approximately two-fold in the adult subjects, while in the pediatric group it was only approximately 64% of the controls (9.09% in the adults, 2.63% in pediatric patients, and 4.08% in the controls). No accumulation of the OCTN variants was observed in any patient group versus the controls.CONCLUSION: The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high and the profile differs from the adult CD patients, whereas the results for SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD.

Involvement of serum retinoids and Leiden mutation in patients with esophageal, gastric, liver, pancreatic, and colorectal cancers in Hungary

AIM: To analyze the serum levels of retinoids and Leiden mutation in patients with esophageal, gastric, liver,pancreatic, and colorectal cancers.METHODS: The changes in serum levels of retinoids (vitamin A, α- and β-carotene, α- and β-cryptoxanthin,zeaxanthin, lutein) and Leiden mutation were measured by high liquid performance chromatography (HPLC)and polymerase chain reaction (PCR) in 107 patients (70 males/37 females) with esophageal (0/8), gastric (16/5), liver (8/7), pancreatic (6/4), and colorectal (30/21including 9 patients suffering from in situ colon cancer)cancer. Fifty-seven healthy subjects (in matched groups)for controls of serum retinoids and 600 healthy blood donors for Leiden mutation were used.RESULTS: The serum levels of vitamin A and zeaxanthin were decreased significantly in all groups of patients with gastrointestinal (GI) tumors except for vitamin A in patients with pancreatic cancer. No changes were obtained in the serum levels of α- and β-carotene,α- and β-cryptoxanthin, zeaxanthin, lutein in patients with GI cancer. The prevalence of Leiden mutation significantly increased in all groups of patients with GI cancer.CONCLUSION: Retinoids (as environmental factors)are decreased significantly with increased prevalence of Leiden mutation (as a genetic factor) in patients before the clinical manifestation of histologically different (planocellular and hepatocellular carcinoma, and adenocarcinoma) GI cancer.