Hyperlipemia pancreatitis onset time affects the association between elevated serum triglyceride levels and disease severity.

BACKGROUND: The association of serum triglyceride (TG) levels with the severity of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains controversial. This study aimed to comprehensively assess the TG levels from the initial onset and their predictive value in the disease assessment of HTG-AP. METHODS: Data collected from January 2018 to July 2021 in one institute were assessed retrospectively. HTG-AP was defined as a TG level > 500 mg/dL in the absence of other common aetiologies of AP. The TG levels within 24 hours (24 h), 48 hours (48 h), 3-4 days (3-4 d), and 5-7 days (5-7 d) after symptom onset and their correlations with disease severity in HTG-AP patients were analysed by cross-sectional and longitudinal studies. RESULTS: In the cross-sectional study, 377 HTG-AP patients were included before lipid-lowering intervention: 216 subjects had their first TG levels measured within 24 h after onset, 91 within 48 h, 50 in 3-4 d, and 20 in 5-7 d. TG levels decreased in the 24 h, 48 h and 3-4 d groups (P < 0.001), however, the TG decline in the 5-7 d group had no difference compared with the 3-4 d group. HTG-AP patients with severe or moderately severe disease displayed higher TG levels than those with mild disease in the 24 h and 48 h groups (P < 0.050) but not in the 3-4 d or 5-7 d groups. Furthermore, the TG levels were correlated with the modified computed tomography severity index only in the 24 h and 48 h groups, while an association between serum calcium levels and C-reactive protein levels was only present in the 24 h group. Similarly, the TG levels were related to hospital days and ICU days in the 24 h and/or 48 h groups. In the longitudinal study, 165 patients with complete records of TG levels from 24 h to 5-7 d were enrolled. With supportive care and lipid-lowering treatment after admission, the TG levels declined rapidly (P < 0.001), and the correlations with disease severity weakened or even disappeared from 24 h to 5-7 d. CONCLUSION: TG levels decreased and attenuated the association with disease severity of HTG-AP over the time of onset. The TG levels within the initial 48 h after onset were most useful for the diagnosis and disease assessment of HTG-AP.

Association of Crohn's disease with Foxp3 gene polymorphisms and its colonic expression in Chinese patients.

BACKGROUND: Fork head/winged helix transcription factor (Foxp3) plays a pivotal role in regulatory T (Treg) cells. The present study aimed to assess the association of Crohn's disease (CD) with Foxp3 polymorphisms and its colonic expression in Chinese patients. METHODS: The Foxp3 polymorphisms, rs3761547, rs2232365, rs2294021, and rs3761548, were examined by SNaPshot in 268 CD patients and 490 controls. The colonic expression levels of Foxp3, IL-2, and IL-4 were detected in 31 CD patients and 31 controls using real-time quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Compared to male controls, the proportion of variant allele of rs3761547 was increased in male patients. The variant alleles of rs3761547, rs2232365, and rs2294021 were less in male patients with stricturing CD compared to those with non-stricturing, non-penetrating CD; however, these variants were frequently detected in male patients with colonic CD than in those with ileocolonic CD. The variant allele of rs3761548 was increased in male patients with penetrating CD compared to those with non-stricturing, non-penetrating CD. The colonic expression of Foxp3 was higher in CD patients than in controls (both males and females). Compared to male patients carrying wild-type alleles, the colonic expression of Foxp3 was downregulated in male patients with variant alleles, rs3761547, rs2232365, rs2294021, and rs3761548, respectively. However, the Foxp3 polymorphisms were not significantly related with the colonic expression levels of IL-2 and IL-4 in CD patients (both males and females). CONCLUSION: Foxp3 polymorphisms might increase the CD susceptibility by reducing the colonic expression of Foxp3 in male patients.

Association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with Crohn's disease in Chinese patients.

BACKGROUND AND AIM: The vitamin D receptor (VDR) regulates immune responses and inflammation through binding with 1,25-dihydroxyvitamin D, the active form of vitamin D. The serum 25-hydroxyvitamin D (25(OH)D) level clinically reflects vitamin D status in the human body. We investigated the association of VDR polymorphisms and 25(OH)D levels in Chinese patients with Crohn's disease (CD). METHODS: Vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) were genotyped by SNaPshot. Serum 25(OH)D levels were measured by electro-chemiluminescence immunoassay. RESULTS: A total of 297 patients with CD and 446 controls were recruited. Compared with controls, mutant alleles and genotypes of BsmI and TaqI were less prevalent in patients with CD (all P < 0.05/4 = 0.0125). The AAC haplotype formed by BsmI, ApaI, and TaqI was also less prevalent in patients with CD (P = 0.004). Furthermore, 124 patients and 188 controls were randomly selected for measurements of 25(OH)D levels. Average 25(OH)D level was lower in patients with CD than in controls (15.46 ± 8.11 vs 21.64 ± 9.45 ng/mL, P < 0.001) and negatively linked to CD activity index (ß = -0.829, P < 0.001), platelet count (ß = -0.253, P < 0.001) and neutrophil percentage (ß = -0.136, P = 0.005) in patients with CD. The ApaI mutant genotype and vitamin D deficiency (<20 ng/mL) were independently associated with CD (P = 0.009, P < 0.001, respectively). In patients with CD, vitamin D deficiency interacted with FokI, ApaI, and TaqI mutant genotypes (P = 0.027, P = 0.024, and P = 0.040, respectively). CONCLUSIONS: Vitamin D receptor (BsmI, ApaI, and TaqI) mutations and lower 25(OH)D levels are associated with CD in Chinese patients. Moreover, VDR (FokI, ApaI, and TaqI) mutations and vitamin D deficiency may have a combined impact on CD.

[Analysis of single nucleotide polymorphisms and haplotypes of FCGR2A gene among patients with ulcerative colitis].

OBJECTIVE: To assess the association of several single nucleotide polymorphisms and haplotypes of the FCGR2A gene with ulcerative colitis (UC) among Chinese patients. METHODS: For 198 UC patients and 356 healthy controls, the alleles and genotypes of the FCGR2A gene (rs1801274, rs10800309 and rs6696854) were detected with a multiplex SNaPshot technique. All subjects were also subjected to linkage disequilibrium and haplotype analyses. RESULTS: The mutant homozygote (CC) of the FCGR2A gene rs1801274 polymorphism was less frequent among UC patients compared with the controls (5.56% vs. 11.80%, P=0.017, OR=0.440, 95%CI: 0.221-0.875). However, the allelic and genotypic distributions of other two SNPs did not differ significantly between the two groups (all P>0.05). Furthermore, no association of the three SNPs (rs1801274, rs10800309 and rs6696854) of the FCGR2A gene with the severity and location of the UC was found (all P>0.05). The three SNPs were shown to be in a strong linkage [rs1801274-rs10800309 (D'=0.863, r2=0.634); rs1801274-rs6696854 (D'=0.753, r2=0.546); rs10800309-rs6696854(D'=0.990, r2=0.802)]. Moreover, the frequency of T-A-T haplotype was higher among the UC patients compared with the controls (67.40% vs. 60.93%, P=0.032, OR=1.326, 95%CI: 1.024-1.717). CONCLUSION: Our findings suggested that the mutant homozygote (CC) of the FCGR2A gene (rs1801274) may have a protective role among Chinese patients with UC. Moreover, the T-A-T haplotype formed by rs1801274, rs10800309 and rs6696854 may confer a higher risk for UC.

[Associations of Crohn's disease with DR4 and DR5 gene polymorphisms].

OBJECTIVE: To assess the associations of death receptor DR4 and DR5 gene polymorphisms with Crohn's disease (CD). METHODS: A total of 295 CD patients and 490 healthy controls were recruited. Three single nucleotide polymorphisms (SNPs) of the DR4 (rs13278062, rs20575) and DR5 (rs1047266) genes were determined with a SNaPshot method. Unconditional logistic regression analysis was carried out for determining the allelic and genotypic differences of the three SNPs between CD patients and the controls, as well as the influence of the DR4 and DR5 gene polymorphisms on the clinical features of CD patients. Linkage disequilibrium and haplotype analysis were calculated by haplotype 4.2 and R language software. A gene-gene interaction model was established to analyze whether the three SNPs can exert a synergistic effect on the susceptibility to CD. RESULTS: The mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were increased among CD patients compared to the controls (37.12% vs. 32.04%, P = 0.040, 95%CI: 1.010-1.550; 62.71% vs. 54.90%, P = 0.032, 95%CI: 1.028-1.855, respectively). However, the allelic and genotypic frequencies of DR4 (rs20575) and DR5 (rs1047266) did not differ between the two groups (all P > 0.05). Based on the Montreal Classification Standards, the CD patients were stratified by locations and behaviors of the disease. After multiple comparison correction (P < 0.0125), compared to ileocolonic CD patients respectively, the mutant allele (T) and genotype (GT+TT) of the rs13278062 polymorphism were significantly increased in colonic CD patients (41.04% vs. 25.64%, P = 0.002, 95%CI: 0.315-0.778; 66.04% vs. 41.03%, P = 0.001, 95%CI: 0.196-0.655, respectively) and terminal ileum CD patients (41.44% vs. 25.64%, P = 0.002, 95%CI: 0.311-0.762; 74.77% vs. 41.03%, P < 0.001, 95%CI: 0.126-0.437, respectively). In comparison to penetrating CD patients, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were significantly decreased in stricturing CD patients (32.29% vs. 48.91%, P = 0.007, 95%CI: 0.300-0.828; 57.29% vs. 86.96%, P = 0.001, 95%CI: 0.078-0.520, respectively). A similar conclusion was drawn for the mutant genotype (GT+TT) of DR4 (rs13278062) in non-stricturing, non-penetrating CD patients (58.82% vs. 86.96%, P = 0.001, 95%CI: 0.086-0.536). Haplotype analysis indicated that the CT haplotype formed by rs20575 and rs13278062 was increased in CD patients compared to the controls (37.1% vs. 31.8%, P = 0.029, OR=1.279, 95%CI: 1.022-1.600). The outcome of a gene-gene interaction model indicated that the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may play a negatively synergistic role in CD patients (B = - 0.483, OR = 0.617, P = 0.030). CONCLUSION: The rs13278062 polymorphism of the DR4 gene not only can confer an increased risk for CD, but may also influence the location of the lesions and the disease behaviors. The CT haplotype formed by rs20575 and rs13278062 may be an independent risk factor for CD. Furthermore, the mutant genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may exert a negative synergistic effect on CD.

Association between red cell distribution width/serum albumin ratio and diabetic kidney disease.

BACKGROUND: Previous studies have shown that the red cell distribution width (RDW)/serum albumin ratio (RA) is an integrative and new inflammatory marker. RA is associated with clinical outcomes in a variety of diseases, but the clinical value of RDW/RA in the assessment of diabetic kidney disease (DKD) has not been elucidated. We examined the link between diabetic RA and DKD while controlling for a wide variety of possible confounders. METHODS: Retrospective cohort analysis of the National Health and Nutrition Examination Survey (NHANES: 2009-2018) database from the Second Affiliated Hospital and Yuying Children's Hospital and the Wenzhou Medical University (WMU) database was conducted. Multivariate logistic regression analysis was used to assess the association between RA and DKD. RESULTS: Overall, 4513 diabetic patients from the NHANES database (n = 2839) and the WMU (n = 1412) were included in this study; 974 patients were diagnosed with DKD in NHANES and 462 in WMU. In the NHANES cohort, diabetes mellitus (DM) patients with higher RA level had a higher risk of DKD (odds ratio = 1.461, 95% confidence interval: 1.250-1.707, p < 0.00001). After adjusting for confounders and propensity score-matched (PSM) analysis, both shown RA levels were independently linked to DKD (pAdjust = 0.00994, pPSM = 0.02889). Similar results were also observed in the WMU cohort (p < 0.00001). CONCLUSIONS: The study observes that the RA was an independent predictor of DKD in DM patients. The RA, a biomarker that is cost-effective and easy-to-access, may have potential for risk stratification of DKD.

Systemic Immune-Inflammation Index for Predicting the Prognosis of Critically Ill Patients with Acute Pancreatitis.

BACKGROUND: Systemic immune-inflammation index (SII) has been identified as a prognostic biomarker in various diseases. However, its significance in acute pancreatitis (AP) has not been reported. Therefore, the main aim of this study was to determine the association of SII with clinical outcomes of AP patients, after adjusting for several confounders. METHODS: This retrospective cohort study was conducted using data retrieved from the Medical Information Mart for Intensive Care III database (MIMIC-III). The study only included patients diagnosed with AP. SII was calculated as the platelet counts x neutrophil counts/lymphocyte counts. Cox regression models were employed to assess the impact of SII on the 30- and 90-day mortality of AP patients. Subgroup analysis was carried out to explore the stability of the relationship between SII and AP mortality. RESULTS: A total of 513 patients were found to be eligible based on the inclusion and exclusion criteria. For 30-day all-cause mortality, in the model adjusted for multiple confounders, the HR (95% CI) for mid-SII group (SII: 75.6-104.2) and high-SII groups (SII: >104.2) were 1.29 (0.65, 2.56) and 2.57 (1.35, 4.88), respectively, compared to the low-SII group (SII: <75.5). A similar trend was observed for 90-day mortality. Subgroup analyses presented a stable relationship between SII and 30-day all-cause mortality of AP patients. CONCLUSION: SII is a potentially useful prognostic biomarker for AP. However, prospective studies are needed to confirm this finding.

The association between vitamin D receptor polymorphisms and serum 25-hydroxyvitamin D levels with ulcerative colitis in Chinese Han population.

There is now growing evidence suggesting that Vitamin D is playing a critical role in modulating the innate and adaptive immune responses. Several polymorphisms have been identified in the vitamin D receptor (VDR) gene but their association with ulcerative colitis (UC) susceptibility remained controversy. In the current study, we examined the association between VDR polymorphisms and serum level of 25-hydroxyvitamin D [25(OH)D] with UC in Chinese Han population. Polymorphisms of FokI (rs2228570)/BsmI (rs1544410)/ApaI (rs7975232)/TaqI (rs731236) in the VDR gene were assessed in a case-control study comprising 404 UC patients and 612 controls. Moreover, 25(OH)D levels were measured by electro-chemiluminescence immunoassay in 75 UC patients and 120 controls. Our results suggested that BsmI polymorphism frequency was significantly lower in UC patients (P=0.028), and the frequency of AAC haplotype formed by BsmI, ApaI and TaqI was also significantly lower in UC patients (P=0.012). Moreover, FokI polymorphism was more frequently observed in patients with mild and moderate UC as compared to those with severe UC (P=0.001, P<0.001, respectively). Average 25(OH)D level was lower in UC patients than in controls (19.3±6.8 vs. 21.8±7.3ng/mL, P=0.017), and was significantly correlated with hemoglobin (ß=0.49, P<0.001), C-reactive protein (ß=-0.36, P<0.001), severity of UC (ß=-0.21, P=0.025) and FokI polymorphism (ß=-0.20, P=0.031) in UC patients. Interestingly, there was a significant correlation between FokI polymorphism and vitamin D deficiency (<20ng/mL) in UC patients (P=0.006). Together, these results supported that VDR polymorphisms and 25(OH)D level were significantly correlated with UC risk and severity in Chinese Han population.

Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China.

OBJECTIVES: Dysbiosis of intestinal microbiota has been implicated in ulcerative colitis (UC). Fucosyltransferase (FUT) 2 and FUT3 determine expression of histo-blood group antigens in the gut and may affect the intestinal microbiota. We investigated the association between FUT2 and FUT3 polymorphisms and UC in Chinese patients. METHODS: We genotyped FUT2 (rs281377, rs1047781 and rs601338) and FUT3 (rs28362459, rs3745635 and rs3894326) in 485 UC patients and 580 healthy controls using SNaPshot. We also evaluated expression of Lewis a and b antigens in the sigmoid colon of 7 UC patients and 7 patients with benign colonic polyps. RESULTS: The frequencies of mutant allele (A) and genotype (GA+AA) in FUT3 (rs3745635) were higher in UC patients than controls (P = 0.016, 95%CI: 1.339-1.699; P = 0.038, 95%CI: 1.330-1.742, respectively). Stratified analyses revealed that the frequencies of mutant allele (G) and genotype (TG+GG) of FUT3 (rs28362459) were significantly lower in patients with extensive colitis than those with distal colitis (P<0.001, 95%CI: 0.503-0.742; P = 0.001, 95%CI: 0.567-0.786, respectively). Similar conclusions were drawn for the mutant allele (A) and genotype (GA+AA) of FUT3 (rs3745635) in patients with extensive colitis compared to those with distal colitis (P = 0.006, 95%CI: 0.553-0.845; P = 0.011, 95%CI: 0.621-0.900, respectively). Although expression of Lewis b antigen in the sigmoid colon did not differ between UC patients and controls, Lewis a antigen expression was higher in the cryptic epithelium of both inflammatory and non-inflammatory sigmoid colon of UC patients than controls (P = 0.028). CONCLUSIONS: Our findings indicated that polymorphisms in FUT3 and its intestinal expression might be associated with UC pathogenesis.