OBJECTIVE:To evaluate comprehensively the association of cytotoxic T-lymphocyte antigen 4 (CTLA-4) +49A/G polymorphism with susceptibility to primary biliary cirrhosis (PBC). METHODS:PubMed was used to search for the relevant published articles. The risk of PBC association with the CTLA-4 +49A/G polymorphism was estimated for each study in a random-effects model. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each study. Risks to PBC were estimated by stratified analysis in patients with different ethnicity and antimitochondrial antibody (AMA) status, as well as histological stages. RESULTS:A total of 12 articles were included in the study. An association between PBC and CTLA-4 G allele was found, overall OR = 1.20, 95% CI 1.03-1.41 (P = 0.02). However, stratification by ethnicity indicated a significant association between the G allele and PBC in Asians (OR = 1.36, 95% CI 1.12-1.65, P = 0.002), but not in Caucasians (OR = 1.15, 95% CI 0.95-1.39, P = 0.15). Moreover, AMA positive patients carrying G allele were more susceptible to PBC compared with AMA negative patients (OR = 1.23, 95% CI 1.06-1.43, P = 0.007; OR = 0.98, 95% CI 0.71-1.34, P = 0.88, respectively). CONCLUSIONS:Polymorphism in exon 1 of CTLA-4 gene at position 49 may act as a candidate of susceptibility locus to PBC. However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.KEY WORDS: cytotoxic T-lymphocyte antigen 4, single nucleotide polymorphism, primary biliary cirrhosis, meta-analysis. INTRODUCTIONPrimary biliary cirrhosis (PBC) is an autoimmune disease characterized by female preponderance and destruction of intrahepatic bile ducts that often results in cirrhosis and hepatic failure. [1][2][3][4] Twin and family aggregated data suggest that there is a significant genetic predisposition for PBC, and the complex features in etiology are thought to be resulted from the interaction between multiple genetic and environmental factors. 2011; 12; 428-435 doi: 10.1111/j.1751-2980.2011.00537.x 428 Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative regulator of T-cell immune response and is expressed predominantly in activated regulatory T-cells. [6][7][8] The absence of gene in knockout or CTLA-4-deficient mice leads to massive lymphoproliferative disorders, fatal multi-organ destruction and early death. Journal of Digestive Diseases2,3 The apparent association between pathological T-cell response and the development of PBC 9,10 suggests that CTLA-4 might be an attractive and candidate facilitator of the PBC susceptibility gene. Variants in the gene encoding immunoregulatory CTLA-4 were examined for the candidate susceptibility loci for PBC.CTLA-4 gene is located on chromosome 2q33; the adjacent gene encoding another two immunoregulatory proteins: inducible co-stimulator and its stimulatory counterpart (CD28).11 Significant amino-acid replacement resulted from single nucleotide polymorphisms (SNPs) has been described. For ...

BackgroundWe assessed levels of circulating amino acids in different etiologies of chronic kidney disease (CKD) and the association of amino acids with risk factors of CKD progression.Material/MethodsHigh-performance liquid chromatography-based analysis was used to determine amino acid profiles in patients with diabetic nephropathy (DN, n=20), hypertensive nephropathy (HN, n=26), and chronic nephritis (CN, n=33), and in healthy controls (HC, n=25).ResultsAll 3 types of CKD patients displayed decreased serum levels of serine, glycine, GABA, and tryptophan compared with healthy controls. Moreover, serine and tryptophan were positively correlated with glucose in DN cohorts. Total cholesterol was positively correlated with tryptophan levels in the DN cohort and negatively correlated with serine levels in the CN cohort. In the HN cohort, glycine was negatively correlated with triglyceride levels, and systolic blood pressure (SBP) was negatively correlated with GABA levels.ConclusionsPatients with different etiologies of CKD have significantly different amino acids profiles, and this indicates specific supplementary nutritional needs in CKD patients.