Ji-Min Zhu

Association of NFKB1 -94ins/delATTG promoter polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis.

The aim of our study is to assess the association of NFKB1 -94ins/delATTG promoter polymorphism with autoimmune and inflammatory diseases using a meta-analysis. We surveyed the studies on the association of NFKB1 -94ins/delATTG promoter polymorphism with autoimmune and inflammatory diseases. Meta-analysis was performed for genotypes DD vs WW, WD vs WW, DD vs WW + WD, WD + DD vs WW, and D allele vs W allele in a fixed/random effect model. Seventeen studies (7312 cases and 6193 controls) were identified. When all groups were pooled, we found no association between NFKB1 -94ins/delATTG promoter polymorphism and autoimmune and inflammatory diseases. In ethnic subgroup analyses, we found no association between NFKB1 -94ins/delATTG promoter polymorphism and autoimmune and inflammatory diseases in the Caucasian population. However, an association of NFKB1 -94ins/delATTG promoter polymorphism with autoimmune and inflammatory diseases was found in the Asian population [D vs W: odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.77-0.99, P = 0.03; WD + DD vs WW: OR = 0.79, 95% CI = 0.65-0.95, P = 0.01; DD vs WW + WD: OR = 0.92, 95% CI = 0.73-1.16, P = 0.11; DD vs WW: OR = 0.80, 95% CI = 0.62-1.03, P = 0.09; WD vs WW: OR = 0.78, 95% CI = 0.65-0.95, P = 0.01]. In disease subgroup analyses, we found no association between NFKB1 -94ins/delATTG promoter polymorphism and inflammatory bowel disease, ankylosing spondylitis and Graves disease. This meta-analysis suggests a possible association between NFKB1 -94ins/delATTG promoter polymorphism and certain autoimmune and inflammatory diseases in the Asian population, but not in the Caucasian population. This finding demands further investigation.

Association of the − 1082G/A polymorphism in the interleukin-10 gene with systemic lupus erythematosus: A meta-analysis

A great many studies have investigated the -1082G/A polymorphism (rs1800896) in the interleukin-10 gene (IL10) with SLE susceptibility, but the results are inconsistent and inconclusive. The aim of this meta-analysis was in order to more precisely estimate the relationship. The databases of Pubmed and Web of Science updated to Oct, 2012 were retrieved. Odds ratio (OR) and corresponding 95% confidence interval (95%CI.) as effect size were calculated by fixed-effect model. Analysis for allele contrast of stratification by ethnicity in either Asian or Caucasian, as well as in overall population indicated no significant association (Overall: OR 1.096, 95%CI. 0.995-1.207; Asian: OR 1.204, 95%CI.: 0.944-1.535; Caucasian: OR 1.075, 95%CI.: 0.961-1.202). Analysis for recessive model showed no association in overall populations and in Caucasian (Overall: OR 1.135, 95%CI.: 0.945-1.362; Caucasian: OR 1.069, 95%CI.: 0.882-1.296), but significant association in Asian (OR: 2.848; 95%CI.: 1.194-6.791). Analysis for dominant model indicated that the variant G allele carriers (GG+GA) may have increased the risk of SLE when compared with the homozygote AA in overall populations and in Caucasian (Overall: OR 1.203, 95%CI.: 1.029-1.407; Caucasian: OR 1.233, 95%CI.: 1.014-1.499), but not in Asian (OR: 1.154; 95%CI.: 0.856-1.557). Significant association was found by using homozygote contrast model in overall populations and Asian (Overall: OR 1.303, 95%CI.: 1.031-1.648; Asian: OR 3.206, 95%CI.: 1.241-8.284), while no association was found in Caucasian (OR: 1.209; 95%CI.: 0.940-1.556). The results provided evidence for the association between the IL10 -1082G/A polymorphism and the risk of SLE. To confirm these findings, more case-control studies with subtle study design based on adequately sized populations are required.

Association of the interleukin-10 -592A/C, -1082G/A and -819T/C gene polymorphisms with type 2 diabetes: a meta-analysis.

There is more evidence that interleukin-10 (IL-10), as a multifunctional regulatory cytokine of inflammatory responses, may have an important role in type 2 diabetes (T2D). However, genetic association studies that evaluated the relationship between IL-10 gene variants and T2D have produced conflicting results. The aim of this study was to determine whether the IL-10 gene polymorphisms (-592A/C, -1082G/A, -819T/C) conferred susceptibility to T2D through a meta-analysis. A comprehensive search was conducted to examine all the eligible studies. A total of 9 studies involving 2838 T2D patients and 2773 controls were considered in the meta-analysis. Overall, there was no significant association between IL-10 -592A/C and T2D (A vs C: OR=0.93, P=0.625; AA+AC vs CC: OR=0.89, P=0.511; AA vs AC+CC: OR=0.93, P=0.821). We failed to find the association between the IL-10 -1082G allele and T2D (OR=1.04, P=0.430), but the genotypes of the IL-10 -1082G/A polymorphism conferred a risk for the development of T2D (GA vs AA: OR=1.21, P=0.027; GG+GA vs AA: OR=1.17, P=0.048). Analysis of the -819T/C polymorphism revealed no significant association with T2D (T vs C: OR=1.04, P=0.853; TT+TC vs CC: OR=1.07, P=0.834; TT vs TC+CC: OR=1.08, P=0.824). In conclusion, the present meta-analysis suggests association between the IL-10 -1082G/A polymorphism and T2D. However, additional well-designed and larger scale primary studies are required to further evaluate the IL-10 gene polymorphisms and T2D.

D18S880 microsatellite polymorphism of carnosinase gene and diabetic nephropathy: a meta-analysis.

OBJECTIVEnThe aim of this study was to determine whether the CNDP1 (carnosinase gene) D18S880 microsatellite polymorphism confers susceptibility to diabetic nephropathy (DN).nnnMETHODSnThe authors conducted meta-analysis on association between the CNDP1 D18S880 microsatellite polymorphism and DN susceptibility, using fixed and random effects models.nnnRESULTSnA total of nine comparative studies were included in this meta-analysis, which included 4546 DN, 7994 diabetes mellitus (DM), and 1826 healthy (Heal) subjects. Overall, the analysis revealed that the D18S880 microsatellite polymorphism was significantly associated with DN for the five trinucleotide repeat (5L) allele and five leucines repeat (5L-5L) homozygous in the comparisons of DN versus DM (5L: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.84-0.97, p=0.008; 5L-5L: OR 0.88, 95% CI 0.81-0.97, p=0.006) and DN versus non-DN (DM+Heal) (5L: OR 0.92, 95% CI 0.86-0.98, p=0.009; 5L-5L: OR 0.89, 95% CI 0.82-0.96, p=0.004). The protective effects of the D18S880 polymorphism were similar to those observed in the subgroups of the type 2 DM and the Caucasian population. However, significant association was not found in the type 1 DM population.nnnCONCLUSIONSnThis meta-analysis confirms that the carnosinase D18S880 microsatellite polymorphism is associated with DN susceptibility, especially in the type 2 DM and the Caucasian population.

Prevalence of systemic lupus erythematosus and risk factors in rural areas of Anhui Province.

AbstractnSystemic lupus erythematosus (SLE) is a severe complex rheumatic disease, but good estimate of its prevalence and risk factors is lacking in China. The aim of the study was to explore the prevalence of SLE and risk factors in rural areas of Anhui Province of China. Eleven counties were randomly selected in Anhui Province, and then, 15xa0% of the villages in selected counties were randomly sampled as study sites. Patients with SLE were identified through two phases. Based on the cases identified, a population-based case–control study was designed to examine risk factors associated with SLE. A total of 1,253,832 individuals and identified 471 SLE cases were surveyed. Crude and age-standardized prevalence were estimated at 37.56 and 36.03 per 100,000 persons, respectively. Gender difference in the prevalence of SLE was significant (Pxa0=xa04.62xa0×xa010−76), and the age-standardized prevalence was 6.17 for males and 67.78 for females per 100,000 persons. The distribution of SLE prevalence was significant by age group (Pxa0=xa01.78xa0×xa010−53), and the peak prevalence was observed at 40–50xa0years. Multiple environmental factors were associated with SLE, including birth conditions, sweet food, cooking oil, taste, fruit consumption, sunlight exposure, quality of sleep, physical activities, drinking water, residence, negative life events, hepatitis B vaccine, age of menarche, and age at birth of first child (Pxa0<xa00.05). Our large population-based epidemiological survey estimated the prevalence of SLE at 37.56 per 100,000 persons. Multiple environmental factors were associated with the development of SLE.

The association of IL1α and IL1β polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis

Many epidemiological studies have investigated IL1α and IL1β polymorphisms with SLE risk, but no conclusions are available because of conflicting results. This meta-analysis was performed to more precisely estimate the relationships. The databases of PubMed updated to September 1st, 2012 were retrieved. Odds ratio (OR) and corresponding 95% confidence interval (95% CI) as effect size were calculated by a fixed- or random-effect model. In total, six case-control studies for IL1β-511C/T, four studies for IL1β+3953C/T, three studies for IL1α-889C/T and three studies for IL1α+4845G/T were involved in this analysis. The results indicated that for IL1α-889C/T polymorphism T allele was associated with decreased risk of SLE (OR (95% CI)) (T vs. C: 0.802 (0.679-0.949); TT+CT vs. CC: 0.615 (0.380-0.995); TT vs. CC: 0.679 (0.466-0.989)). However, when analysis for TT vs. CT+CC was conducted, the result indicated that IL1α-889C/T polymorphism was not associated with SLE (OR (95% CI): 0.847 (0.595-1.205)). Combined analysis indicated that IL1β-511C/T polymorphism was not overall associated with risk of SLE (OR (95% CI)) (T vs. C: 1.113 (0.954-1.298); TT vs. CT+CC: 1.146 (0.889-1.447); TT+CT vs. CC: 1.145 (0.903-1.452); TT vs. CC: 1.255 (0.928-1.698)). When subgroup analysis for Asian ethnicity was conducted, the results indicated that IL1β-511C/T polymorphism was associated with SLE only for TT vs. CT+CC (OR (95% CI): 1.468 (1.001-2.152)), but was not associated for T vs. C (OR (95% CI): 1.214 (0.955-1.544)), TT+CT vs. CC (OR (95% CI): 1.112 (0.765-1.615)) and TT vs.CC (OR (95% CI): 1.411 (0.896-2.222)). In addition, overall analyses indicated that IL1β+3953C/T and IL1α+4845G/C polymorphisms were also not associated with risk of SLE (OR (95% CI)) (for IL1β+3953C/T T vs. C: 0.996 (0.610-1.626), TT vs. CT+CC: 0.658 (0.318-1.358), TT+CT vs. CC: 1.021 (0.618-1.687), TT vs. CC: 0.640 (0.309-1.325); for IL1α+4845G/T T vs. G: 1.067 (0.791-1.440), TT+GT vs. GG: 0.934 (0.646-1.351)).This study inferred that IL1α-889C/T polymorphism might be moderately associated with SLE, but no sufficient evidence was available to support any associations between IL1β+3953C/T or IL1α+4845G/C polymorphisms and SLE. We could not draw a definite conclusion between IL1β-511C/T polymorphism and risk of SLE owing to the limited data. Further large sample-sized studies should be required.

CTLA-4 -1722T/C Polymorphism and Systemic Lupus Erythematosus Susceptibility: A Meta-analysis Involving Ten Separate Studies

Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) -1722T/C polymorphism has been identified as a susceptibile gene for systemic lupus erythematosus (SLE), but studies are inconsistent. To better assess the association between CTLA-4 -1722T/C polymorphism and SLE, a meta-analysis was performed, including 10 studies, total of 1 387 patients and 1 617 controls. Overall, the CTLA-4 -1722T/C polymorphism was significantly associated with SLE susceptibility (T VS C: OR = 1.17, 95% CI = 0.86–1.60, P = 0.304; T/T VS C/C: OR = 1.92, 95% CI = 1.09–3.39, P = 0.024; T/C VS C/C: OR = 1.50, 95% CI = 0.91–2.49, P = 0.114; T/T VS T/C: OR = 1.29, 95% CI = 0.95–1.75, P = 0.107). When stratified by ethnicity, the CTLA-4 -1722T/C polymorphism was associated with SLE only in Asians (T VS C: OR = 1.47, 95% CI = 1.10–1.96, P = 0.010; T/T VS C/C: OR = 2.09, 95% CI = 1.13–3.85, P = 0.018; T/C VS C/C: OR = 1.53, 95% CI = 0.87–2.69, P = 0.141; T/T VS T/C: OR = 1.42, 95% CI = 0.97–2.09, P = 0.070). In summary, the CTLA-4 -1722T/C polymorphism confers to SLE risk, especially in Asians.

Association of SUMO4 M55V polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis.

The purpose of this study was to generate large‐scale evidence on whether SUMO4 M55V polymorphism is associated with autoimmune and inflammatory diseases using a meta‐analysis. We surveyed studies on the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in PubMed. Meta‐analysis was performed for genotypes AG versus AA, GG versus AA, GG versus AAu2003+u2003AG, AGu2003+u2003GG versus AA and G allele versus A allele in a fixed/random effect model. We identified 16 studies (11u2003407 cases and 10u2003679 controls) using PubMed search. When all groups were pooled, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases (G versus A: ORu2003=u20031.11, 95%CIu2003=u20031.03–1.19, Pu2003=u20030.005; AGu2003+u2003GG versus AA: ORu2003=u20031.17, 95%CIu2003=u20031.06–1.28, Pu2003=u20030.001; GG versus AAu2003+u2003AG: ORu2003=u20031.07, 95%CIu2003=u20030.94–1.21, Pu2003=u20030.29; GG versus AA: ORu2003=u20031.15, 95%CIu2003=u20031.00–1.34, Pu2003=u20030.06; AG versus AA: ORu2003=u20031.15, 95%CIu2003=u20031.08–1.23, Pu2003<u20030.0001). In subgroup analyses, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in Asian population (G versus A: ORu2003=u20031.18, 95%CIu2003=u20031.08–1.28, Pu2003=u20030.0001; AGu2003+u2003GG versus AA: ORu2003=u20031.30, 95%CIu2003=u20031.16–1.45, Pu2003<u20030.00001; GG versus AAu2003+u2003AG: ORu2003=u20031.04, 95%CIu2003=u20030.78–1.37, Pu2003=u20030.80; GG versus AA: ORu2003=u20031.20, 95%CIu2003=u20030.99–1.45, Pu2003=u20030.07; AG versus AA: ORu2003=u20031.32, 95%CIu2003=u20031.18–1.49, Pu2003<u20030.00001). But the association was not found in Caucasian population. Meanwhile, an association of SUMO4 M55V polymorphism with autoimmune diabetes was found (G versus A: ORu2003=u20031.18, 95%CIu2003=u20031.08–1.30, Pu2003=u20030.0005; AGu2003+u2003GG versus AA: ORu2003=u20031.22, 95%CIu2003=u20031.13–1.32, Pu2003<u20030.00001; GG versus AAu2003+u2003AG: ORu2003=u20031.15, 95%CIu2003=u20030.96–1.38, Pu2003=u20030.13; GG versus AA: ORu2003=u20031.32, 95%CIu2003=u20031.08–1.60, Pu2003=u20030.006; AG versus AA: ORu2003=u20031.23, 95%CIu2003=u20031.13–1.33, Pu2003<u20030.00001). This meta‐analysis demonstrates the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases, especially in Asian population.

Association study between the TP53 Rs1042522G/C polymorphism and susceptibility to systemic lupus erythematosus in a Chinese Han population

Tumour suppressor protein 53 (p53) plays a central role in apoptosis, cell proliferation and death. Previously studies found contribution of functional p53 Arg72Pro polymorphism (TP53 rs1042522G/C polymorphism) in the development of systemic lupus erythematosus (SLE) remains controversial. In this study, for the first time, we evaluated its association with SLE in a Chinese Han population. This case–control study enrolled 1470 SLE patients and 2283 healthy controls. The genotyping of TP53 rs1042522 polymorphism was determined by Sequenom Mass ARRAY technology. Statistical analysis was conducted by Chi-square test (χ2 test). Odds ratio (OR) with 95% confidence interval (CI) was calculated using unconditional logistic regression with adjusting age and sex. Allele and genotype frequencies of TP53 rs1042522G/C polymorphism showed statistically significant difference between the SLE patients and the normal controls (C vs. G: ORu2009=u20090.89, 95% CI 0.89–0.97, pu2009=u20090.01; (GCu2009+u2009CC) vs. GG using recessive model: ORu2009=u20090.84, 95% CI 0.73–0.96, pu2009=u20090.01; GC vs. GG using co-dominant model: ORu2009=u20090.86, 95% CI 0.74–0.99, pu2009=u20090.04; CC vs. GG using co-dominant model: ORu2009=u20090.80, 95% CI 0.66–0.96, pu2009=u20090.02; GC vs. GG using co-dominant model: ORu2009=u20090.86, 95% CI 0.74–0.99, pu2009=u20090.02). In addition, there was weak association between discoid rash and distribution of TP53 rs1042522G/C polymorphism in SLE patients (C vs. G: ORu2009=u20091.25, 95% CI 1.00–1.55, pu2009=u20090.04; CC vs. GG using co-dominant model: ORu2009=u20091.54, 95% CI 1.10–2.36, pu2009=u20090.04). Our finding suggests a significant relationship between the TP53 rs1042522G/C polymorphism and SLE. TP53 rs1042522G/C polymorphism would be promising as an indicator of SLE as well as the therapeutic target if its functions and mechanisms could be further investigated.