ABSTRACT
【Objective】 To explore the causal association between interleukin (IL) level and constipation by using two-sample Mendelian randomization. 【Methods】 Analyses were performed based on the data from gene-wide association studies (GWAS). Both interleukin and constipation data were obtained from European populations. IL as an exposure variable was obtained from two GWAS data sets: ⅰ. from a genetic map of the human plasma proteome containing 3 301 samples; ⅱ. from a GWAS data set on 90 circulating proteins, containing 30 931 samples. Constipation as an outcome variable was obtained from two GWAS data sets: ⅰ. from Finngene, containing 26919 cases and 282235 controls; ⅱ. from UKBiobank, containing a total of 3 328 cases and 459682 controls. Single nucleotide polymorphisms strongly associated with exposure variables were used as instrumental variables, with inverse variance weighted (IVW) as the main analysis method, MR-egger regression and weighted median method as supplementary evidence for IVW results, and horizontal pleiotropy and heterogeneity were tested to ensure the stability of the results. 【Results】 In both of the two different outcome variables GWAS data, IVW analysis results showed that decreased level of IL-17 receptor C was associated with an increased risk of constipation, with ORs of 0.956 (95% CI: 0.916-0.997, P=0.036‖Finngene) and 0.998 (95% CI: 0.997-0.999, P=0.040‖ukb). Increased level of IL-18 was associated with an increased risk of constipation, with ORs of 1.055 (95% CI: 1.008-1.104, P=0.022‖Finngene) and 1.001 (95% CI: 1.000-1.002, P=0.044‖ukb); while in the Finngene data, the IVW results also suggested that increased levels of IL-2 receptor alpha subunit α and decreased levels of IL-10 and IL-17 were associated with an increased risk of constipation, with ORs of 1.054 (95% CI: 1.001-1.110, P=0.049), 0.945 (95% CI: 0.896-0.996, P=0.035) and 0.934 (95% CI: 0.896-0.997, P=0.040). 【Conclusion】 IL-17 receptor C, IL-18, IL-2 receptor alpha subunit α, IL-10, and IL-17 were causally associated with the risk of constipation.
ABSTRACT
Objective:To retrospectively analyze the BKV infection of recipients after kidney transplantation(RT)and provide references for diagnosing and treating BK virus infection post-RT.Methods:From January 1, 2018 to December 31, 2020, clinical and follow-up data were reviewed for 561 RT recipients(cadaveric and living donor kidney)at First Hospital of Jilin University. DNA loading of BK virus in blood and urine was determined by quantitative polymerase chain reaction(qPCR)and kidney allograft biopsy performed. Based upon the results, they are divided into four groups of A (372 cases), high-level BK viruria(group B, 128 cases), BK viremia(group C, 52 cases)and BK virus nephropathy(BKVN)(group D, 9 cases). The variables related to BK virus infection were screened by univariate analysis. Meaningful variables( P<0.1)are incorporated into the multi-factor ordered Logistic regression model for examining the independent risk factors of postoperative BK virus infection. Results:The incidence of high-level BKV viruria is 33.69%(189/561)at 18 months post-RT. The average detection time is(4.2±3.8)months, the incidence of BK viremia 10.87%(61/561)and the average detection time(5.2±3.6)months post-RT. The incidence of BKVN is 1.78%(9/561)and the average detection time(7.0±4.0)months post-RT. Univariate analysis showed that gender, age, immunotherapeutic regimen, history of acute rejection and type of donor are correlated with BKV infection. Multivariate Logistic regression analysis indicated that male recipient( P=0.013), immune maintenance regimen( P<0.001)and history of acute rejection( P=0.002)were independent risk factors for developing postoperative BKV infection. Conclusions:There is a high incidence of BKV infection within 12 months post-RT. Male recipient, history of acute rejection and immune maintenance regimen are independent risk factors for BKV infection post-RT.