Association of IFIH1 rs1990760 polymorphism with susceptibility to autoimmune diseases: A meta-analysis

Abstract

Published data on the association between the IFIH1 rs1990760 polymorphism and multiple autoimmune diseases are controversial and inconclusive. To more precisely estimate the association between the IFIH1 rs1990760 polymorphism and susceptibility to autoimmune diseases, a meta-analysis was conducted. Studies examining the association of the IFIH1 rs1990760 polymorphism with autoimmune diseases were exhaustively searched using PubMed, Web of Science and a review of the references. A total of 19 studies with 26 comparisons including 8 type 1 diabetes (T1D), 5 systemic lupus erythematosus (SLE), 5 Graves’ disease (GD), 2 multiple scleorosis (MS), 2 rheumatoid arthritis (RA), 2 Hashimoto's thyroiditis (HT), 2 autoimmune Addison’s disease (AAD) were available for this meta-analysis. Meta-analysis was performed for genotype T/T?+?T/C (dominant model), genotype T/T (recessive model) and T-allele in fixed or random-effects models. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for T-allele were T1D (OR?=?1.184, 95% CI?=?1.142–1.229), SLE (OR?=?1.143, 95% CI?=?1.073–1.217), MS (OR?=?1.181, 95% CI?=?1.062–1.313) and RA (OR?=?1.115, 95% CI?=?1.004–1.239), respectively. For T1D and SLE, significant association was observed in the population of European ancestry, but not in the Asian population. This meta-analysis demonstrates that the IFIH1 rs1990760 T-allele confers susceptibility to T1D, SLE, MS and RA and suggests that the IFIH1 rs1990760 polymorphism might have no effect on GD and AAD. Our result provides further evidence for the notion of common gene underlying multiple autoimmune diseases.     

Analysis of chosen polymorphisms rs2476601 a/G – PTPN22, rs1990760 C/T – IFIH1, rs179247 a/G – TSHR in pathogenesis of autoimmune thyroid diseases in children

Background: Autoimmune thyroid diseases are multifactorial diseases with a genetic susceptibility and environmental factors. A potential role of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, the interferon-induced helicase domain 1 (IFIH1) gene, the thyroid-stimulating hormone receptor (TSHR) gene polymorphisms on autoimmune thyroid diseases (AITDs) in adults has been established unequivocally, but there is still lack of research articles including group of children.

Objective and hypotheses: To estimate the association of polymorphisms of PTPN22, IFIH1 and TSH-R genes with the pre-disposition to Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in children.

Methods: The study was performed in 142 patients with GD, 57 with HT and 160 healthy volunteers. The three single-nucleotide polymorphisms (SNPs): rs2476601 – PTPN22, rs1990760 – IFIH1 and rs179247 – TSHR were genotyped by TaqMan SNP genotyping assay using the real-time PCR.

Results: Rs2476601 A alleles were more frequent in patients with GD in comparison to healthy subjects (p?=?.009 with odds ratio [OR]?=?2.13). Rs2476601 A alleles were more frequent in patients with HT in comparison to healthy subjects (p?=?.008, OR?=?2.48). Rs1990760 T alleles were more frequent in male patients with GD in comparison to healthy males (p?=?.003, OR?=?3.00). In case of HT patients, rs1990760 T alleles were also more frequent in males compared to healthy subjects (p?=?.086, OR =2.47). Rs179247 A alleles were more frequent in patients with GD in comparison to healthy subjects (p?=?0.039, OR?=?1.51).

Conclusions: Rs2476601 A/G, Rs1990760 C/T and Rs179247 A/G polymorphisms could contribute to the development of AITDs in children. The main risk factor for rs2476601 and rs179247 is allele A. In case of rs1990760, the main risk factor is allele T.     

Association Study of IFIH1 rs1990760 Polymorphism with Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a complex autoimmune disease arising from the action of multiple genetic and environmental risk factors. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs1990760, of the interferon induced with helicase C domain 1 (IFIH1) gene with SLE in a Chinese population. A total of 877 SLE patients and 978 healthy control subjects were enrolled in the present study. The genotype of the IFIH1 rs1990760 polymorphism was determined by Sequenom MassARRAY technology. The IFIH1 rs1990760 T allele was significantly increased in patient group compared with control subjects (T versus C, Odds ratio?=?1.20, 95 % confidence interval?=?1.02–1.40). However, no significant difference in genotype distribution was found between cases and controls (P?=?0.07). No significant evidence was detected for the association of the IFIH1 rs1990760 polymorphism with SLE under neither dominant nor recessive model (TT + TC versus CC, P?=?0.06; TT versus TC + CC, P?=?0.08). We also analyzed the association of the IFIH1 rs1990760 T allele with clinical features, whereas no significant signal was found. In conclusion, our study represents the first report demonstrating an association of the IFIH1 rs1990760 polymorphism with SLE susceptibility in a Chinese population.     

IFIH1-GCA-KCNH7 locus is not associated with genetic susceptibility to multiple sclerosis in French patients

A recent investigation reported, for the first time, an association between variants in the IFIH1-GCA-KCNH7 locus and multiple sclerosis (MS). We sought to replicate this genetic association in MS with a new independent MS cohort composed of French Caucasian MS trio families. The two most significant IFIH1 single nucleotide polymorphisms, rs1990760 and rs2068330, reported as involved in MS susceptibility, were genotyped in 591 French Caucasian MS trio families, and analyzed using the transmission/disequilibrium test. No association with MS was found (rs1990760, P=0.45 and rs2068330, P=0.27). Similarly, no significant association was detected after stratification for HLA-DRB1^*1501 carriers. Reasons that may explain this discrepancy between the original report and our study are discussed.     

Genetic variants in IFIH1 play opposite roles in the pathogenesis of psoriasis and chronic periodontitis

The IFIH1 gene is a key factor connecting environmental and genetic factors in the pathogenesis of immune-related diseases. We aimed to investigate whether it has effects on psoriasis, chronic periodontitis and skin test-positive penicillin allergy and to confirm whether these diseases have shared molecular mechanisms originating from shared genetics. Two common variants in IFIH1 were genotyped in 561 patients with psoriasis, 421 patients with chronic periodontitis, 175 patients with skin test-positive penicillin allergy and 1100 shared controls. Then, case-control study was used to analyse the association between IFIH1 and the three diseases. The allele distributions of rs1990760 and rs3747517 in the Chinese population are much different from the European population. The A allele of rs1990760 (OR = 1.30, P = 5.4 × 10(-3)) and A-G (rs1990760/rs3747517) haplotype (OR = 1.31, P = 3.8 × 10(-3)) were highly associated with the risk of psoriasis. However, the A allele of rs1990760 (OR = 0.73, P = 7.8 × 10(-3)) and A-G haplotype (OR = 0.71, P = 4.5 × 10(-3)) were identified as protective factors for chronic periodontitis. IFIH1 affects several immune-related diseases, including psoriasis and chronic periodontitis, and provides a molecular link between genetic susceptibility, viral infections and immune-related diseases. Moreover, we also confirm the hypothesis that shared molecular mechanisms from common genetic variants contribute to a spectrum of immune-related diseases.     

IFIH1 gene polymorphisms in type 1 diabetes: genetic association analysis and genotype-phenotype correlation in Chinese Han population

The evaluation of susceptibility loci is an important addition to the current predictive and screening models in type 1 diabetes of Chinese Han population. Therefore, the aim of this study is to provide evidence for the association between type 1 diabetes and two polymorphisms (rs3747517, rs1990760) from interferon induced with helicase C domain 1 (IFIH1). Here, 464 Type 1 diabetes patients and 465 control subjects were genotyped for these 2 polymorphisms. The results indicated that the allelic frequencies of rs3747517 revealed a strong association with type 1 diabetes risk (P < 0.001); yet, no significant association was observed on rs1990760(P = 0.76). Furthermore, IFIH1 rs3747517 polymorphism had no influence on the positive rates of pancreatic auto-antibodies, and both of the polymorphisms had no interaction with HLA class I-linked risk or phenotypes. In conclusion, IFIH1 rs3747517, but not rs1990760 polymorphism, plays an important role in type 1 diabetes risk in Chinese Han population.     

The rs1990760 polymorphism within the IFIH1 locus is not associated with Graves' disease, Hashimoto's thyroiditis and Addison's disease

Background  

Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD).     

IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells

Genome-wide association (GWA) studies revealed a number of singlenucleotide polymorphisms (SNPs) significantly associated withtype 1 diabetes (T1D). In an attempt to confirm some of thesecandidate associations, we genotyped 2046 Caucasian patientsand 2417 normal controls from the United States for SNPs infive genomic regions. While no evidence was obtained for fourgenomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543on chromosome 19), we provide strong evidence for associationbetween T1D and multiple SNPs in the IFIH1 linkage disequilibrium(LD) block on chromosome 2q. Among the 10 SNPs genotyped forthe 2q region, four SNPs located within the IFIH1 gene or atthe 5' region of IFIH1 showed significant association with T1Din the Georgia population [odds ratio (OR) = 1.7–1.9]with the best P-value found at SNP rs1990760 (P = 8 x 10^–8and OR = 1.9). Several SNPs outside of the IFIH1 gene also showedsignificant but weaker associations. Furthermore, IFIH1 geneexpression levels in peripheral blood mononuclear cells aresignificantly correlated with IFIH1 genotypes, and higher IFIH1levels are found in individuals with the susceptible genotypes(P = 0.005). Thus, both genetic association and gene expressiondata suggest that IFIH1 is the most plausible candidate geneimplicated in T1D in this LD block.     

A polymorphism in melanoma differentiation-associated gene 5 may be a risk factor for enterovirus 71 infection

Enterovirus 71 (EV71) infection has a wide variety of clinical manifestations, from no symptoms to fatal disease. Host immune response may be a determinant of disease severity. We investigated the association of polymorphisms in three pattern recognition receptor (PRR) genes—toll-like receptor 3 (TLR3) (rs3775291), retinoic acid-inducible gene I (RIG-I) (rs10813831) and melanoma differentiation-associated gene 5 (MDA5) (rs1990760)—with the severity of EV71 infection. Polymorphisms of candidate genes in 87 EV71-infected patients and 57 asymptomatic controls were detected. Binary logistic regression analysis revealed statistically significant differences in polymorphism of MDA5 (rs1990760) between patients with severe EV71 infection and asymptomatic controls in an additive model (OR 0.424, 95% CI 0.213-0.845, p 0.015) and a dominant model (OR 0.256, 95% CI 0.103-0.635, p 0.003). Polymorphism of MDA5 (rs1990760) (OR 0.399, 95% CI 0.199-0.798, p 0.009) was found to be associated with the severity of EV71 infection with the analysis of ordinal logistic regression. These results indicated the association between MDA5 (rs1990760) polymorphism and an increased risk of a severe EV71 infection in Chinese children, which offers potential for investigating the innate immune mechanism of EV71 infection and identifying at-risk infants, for whom a preventive strategy may reduce the severity of EV71 infection.     

Association of innate immune IFIH1 gene polymorphisms with dilated cardiomyopathy in a Chinese population

The interferon-induced helicase C domain-containing protein 1 (IFIH1) is a cytosolic RNA sensor belonging to the pattern-recognition receptor (PPR) family. Activation of PPRs on innate immune cells is widely believed to control the development of virus-induced autoimmunity in myocarditis and subsequent dilated cardiomyopathy (DCM). We conducted a pilot study to test whether single nucleotide polymorphisms (SNPs) in IFIH1 were associated with the risk and prognosis of DCM. The TaqMan SNP Genotyping Assay was used to genotype rs1990760 and rs3747517 in 351 DCM patients and 359 controls. The frequency of T allele and CT/TT genotypes at rs1990760 were significantly increased in DCM patients compared to control subjects (p?=?0.046 and p?=?0.027, respectively). The CC homozygosity was associated with worse prognosis expressed by the endpoint of cardiac death compared with allele T carriers of rs3747517 in both univariable (p?=?0.04) and multivariable survival analysis after adjusting for age, sex, left ventricular end-diastolic diameter and ejection fraction (p?=?0.01). The results revealed that rs1990760 was associated with susceptibility to DCM and rs3747517 played a role in the prognostic assessment of DCM, reflecting the distinct genetic contributions of innate IFIH1 polymorphisms in controlling the onset and outcome of DCM.     

Analysis of chosen SNVs in GPC5, CD58 and IRF8 genes in multiple sclerosis patients

PurposeMultiple sclerosis (MS) is an autoimmune disease of the central nervous system with a neurodegenerative compound. Heterogenetic background of autoimmunity pathway components has been suggested in the MS pathogenesis. The main aim of our study was to evaluate the association between selected polymorphisms of theCD58, IRF8 and GPC5 genes and treatment effectiveness in a group of relapsing-remitting MS patients. This is the first study of MS patients from Podlaskie Region in the Polish population.Materials and methodsThe study group comprised 174 relapsing-remitting MS patients diagnosed under 40 years of age. Genotyping was performed using ready to use TaqMan assays.ResultsWe demonstrate a strong association of the polymorphisms with sex, age of onset and response to the treatment applied. A significant correlation was observed in the presence of allele T of rs10492503 polymorphism inGPC5 gene with sex and age of MS onset. Logistic regression analysis revealed an increased risk of the interaction of rs17445836 in IRF8 gene with male sex and the type of treatment (OR = 3.80, p < 0.05), and a decreased risk in the interaction of female sex with disease progress according to the EDSS scale (OR=-2.33, p < 0.05).ConclusionsThe analysis of the correlation between different alleles, genotypes and clinical status confirmed the interaction between the genetic factors of age of onset and response to therapy. The study suggests that genetic variants inGPC5, CD58 and IRF8 genes may be of clinical interest in MS as predictors of age of onset and response to therapy.     

IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk

A recent genome-wide scan of nonsynonymous SNPs and ulterior validation in case-control and family analyses evidenced a susceptibility locus for type 1 diabetes (T1D) on chromosome 2q24.3. We aimed at testing the effect of this locus in other autoimmune diseases with complex genetic background, such as multiple sclerosis (MS). Four SNPs along the locus, rs13422767, rs2111485, rs1990760 and rs2068330, were genotyped using TaqMan MGB chemistry in 311 T1D and 412 MS patients and 535 ethnically matched healthy controls. The previously reported association of this locus was found for the first time in MS (rs2068330, G vs C: P=0.001; OR (95% CI)=0.73 (0.6-0.88)) and a trend for replication was observed in our Spanish diabetic cohort. Therefore, genes included in this locus - IFIH1 interferon induced helicase, GCA grancalcin or the potassium channel KCNH7 - are potential candidates implicated in the pathogenesis of these autoimmune diseases, although strong linkage disequilibrium in the region hampered further localization of the etiologic gene.     

Non-HLA gene effects on the disease process of type 1 diabetes: From HLA susceptibility to overt disease

In addition to the HLA region numerous other gene loci have shown association with type 1 diabetes. How these polymorphisms exert their function has not been comprehensively described, however. We assessed the effect of 39 single nucleotide polymorphisms (SNP) on the development of autoantibody positivity, on progression from autoantibody positivity to clinical disease and on the specificity of the antibody initiating the autoimmune process in 521 autoantibody-positive and 989 control children from a follow-up study starting from birth. Interestingly, PTPN2 rs45450798 gene polymorphism was observed to strongly affect the progression rate of beta-cell destruction after the appearance of humoral beta-cell autoimmunity. Moreover, primary autoantigen dependent associations were also observed as effect of the IKZF4-ERBB3 region on the progression rate of β-cell destruction was restricted to children with GAD antibodies as their first autoantibody whereas the effect of the INS rs 689 polymorphism was observed among subjects with insulin as the primary autoantigen. In the whole study cohort, INS rs689, PTPN22 rs2476601 and IFIH1 rs1990760 polymorphisms were associated with the appearance of beta-cell autoantibodies. These findings provide new insights into the role of genetic factors implicated in the pathogenesis of type 1 diabetes. The effect of some of the gene variants is restricted to control the initiation of β-cell autoimmunity whereas others modify the destruction rate of the β-cells. Furthermore, signs of primary autoantigen-related pathways were detected.     

IFIH1 gene polymorphisms in type 1 diabetes: Genetic association analysis and genotype–phenotype correlation in the Belgian population

The evaluation of susceptibility loci in a registry-based setting could be an important addition to the current predictive and screening models in T1D. Therefore, the aim of this study was to evaluate the importance of one of these loci, IFIH1. T1D patients (n=1981), control subjects (n=2092) and 430 families were genotyped for HLA-DQ and IFIH1 nsSNP rs1990760 (Ala946Thr). In the association analysis, the allelic frequencies, A (62.4% vs. 61.3%) and G (37.6% vs. 38.7%) were similar in cases and controls (χ² = 0.98, p = 0.32), the genotypic frequencies reveals a weak association with T1D (χ² = 6.79, p = 0.03), no significant transmission distortions in families (%T; A = 51.4%, G = 48.0 %, χ² = 1.76, p = 0.19) and no interaction with HLA-DQ-linked risk. Furthermore, no genotype-phenotype correlation was observed. In conclusion, IFIH1 has no important role in T1D risk assessment in a registry-based Belgian population.     

Association of polymorphic variants of IL-1β and IL-1RN genes in the development of Graves’ disease in Kashmiri population (North India)

Purpose

Graves’ disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1β has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1β gene promoter region (?511?T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population.

The association between rs1893217, rs478582 in PTPN2 and T1D risk with different diagnosed age,and related clinical characteristics in Chinese Han population

Objective: To investigate the association between polymorphisms in PTPN2 (rs1893217 and rs478582) and type 1 diabetes (T1D) risk with different diagnosed age, as well as related clinical characteristics in Chinese Han population.

Methods: A total of 2270 Chinese Han individuals (1023 T1D patients and 1247 healthy controls) were genotyped for rs1893217 and rs478582. And 306 newly diagnosed T1D patients were measured for C-peptide levels based on a standard mixed-meal tolerance test. In addition, 40 healthy controls were analyzed for different T cell subsets by multi-color flow cytometry.

Results: Neither rs1893217 nor rs478582 showed any association with T1D risk under an additive model. Stratified analysis for T1D diagnosed age revealed that rs1893217, but not rs478582, was significantly associated with T1D patients diagnosed age ≤18 (OR =0.80, 95% CI: 0.67–0.97, p?=?0.02). For those diagnosed age >18, neither of them showed any association. We also found that rs1893217 had a higher positive rate of ZnT8A (CC vs. TT carrier, OR = 2.07, 95% CI: 1.07–4.03, p?=?0.026) and IA-2A (CT vs. TT carrier, OR = 1.36, 95% CI: 1.02–1.80, p?=?0.038). Furthermore, for rs478582, compared with TT, healthy individuals carrying CC/CT carriers had significantly lower frequency and Helios expression of naive Treg subsets (p?=?0.049 and 0.048 respectively), but not secreting or activating Treg subsets. In addition, we did not find any association between these two polymorphisms and residual β-cell function in newly diagnosed T1D patients.

Conclusions: Our results suggest that rs1893217 may increase the risk of early-onset T1D and affect humoral immunity, while rs478582 may affect Treg subsets.     

The functional polymorphisms of VDR,GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases

Vitamin D is a multi-functional immune regulator, and a low serum concentration of vitamin D promotes autoimmune inflammation. In this study, we evaluate the association between the prognosis of autoimmune thyroid disease (AITD) and the functional polymorphisms of genes that regulate vitamin D metabolism. For 139 Graves’ disease (GD) patients, 116 Hashimoto''s disease (HD) patients and 76 control subjects, we genotyped the following polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP): vitamin D receptor (VDR): rs731236, rs7975232, rs2228570 and rs1544410; group-specific component (GC): rs7041 and rs4588; and CYP2R1: rs10741657. The frequency of the TT genotype for the rs731236 polymorphism was higher in GD patients than in HD patients (P = 0·0147). The frequency of the C allele for the rs7975232 polymorphism was higher in GD patients than in control subjects (P = 0·0349). The proportion of GD patients whose anti-thyrotrophin receptor antibody (TRAb) level was >51% was higher in those with the CC genotype than in those with the CA+AA genotypes (P = 0·0065). The frequency of the CC genotype for the rs2228570 polymorphism was higher in HD patients than in control subjects (P = 0·0174) and GD patients (P = 0·0149). The frequency of the Gc1Gc1 genotype for the GC polymorphism and the AG genotype for the CYP2R1 polymorphism were lower in intractable GD than in GD in remission (P = 0·0093 and 0·0268, respectively). In conclusion, genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be involved with the intractability of GD.     

ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients

The objective of this case-control study was to evaluate the role of four single-nucleotide polymorphisms in the ERAP1 (rs2287987, rs30187, rs27044) and ERAP2 (rs2248374) genes and their haplotypes in predicting the risk for ankylosing spondylitis (AS) on a well-defined Polish population. Our study confirmed the strong association between the HLA-B*27 allele and the disease. For all tested ERAP1 SNPs we found significant differences in the minor allele and genotype distribution between patients and controls. The strongest association with AS was observed for rs30187. The minor T allele and homozygous TT genotype of this SNP significantly increased disease risk (OR = 1.56, 95%CI = 1.22–1.99, p = 0.0004 and OR = 2.52, 95%CI = 1.50–4.25, p = 0.001, respectively). In the case of rs2287987, minor C allele exerted a protective effect (OR = 0.64, 95%CI = 0.46–0.88, p = 0.008). In contrast to ERAP1, we observed no effect of rs2248374 in ERAP2 on the disease. We also carried out ERAP1-ERAP2 haplotype analysis to demonstrate a possible association of both genes with AS. Results showed that the haplotype H4, containing ERAP1 SNPs associated with high enzymatic activity, together with the presence of ERAP2 expression, significantly increased the risk of AS (OR = 1.97, 95% CI = 1.21–3.21, p_corr = 0.048). By contrast, the haplotype H5 coding for low activity of ERAP1 and the lack of ERAP2 expression was strongly protective (OR = 0.41, 95% CI = 0.23–0.72, p_corr = 0.008).     

Impacts of CD152 polymorphisms on cervical cancer susceptibility

AimThe objective of this study was to discuss the effect of CD152 polymorphisms rs231775, rs3087243 and rs5742909 on the susceptibility to cervical cancer.MethodsThe databases of PubMed, EMBASE, Cochrane Library, ISI Web of Science, Google Scholar Web, CNKI and Wanfang were searched for eligible studies. Chi-square-based Q test examined heterogeneity between included studies, and when P_{heterogeneity} was less than 0.05, random-effect model was used to calculate odds ratios (ORs) with their 95 % confidence intervals (95 % CIs); or else, fixed-effect model was selected. Sensitivity analysis was implemented to determine the stability of final results through removing enrolled studies one at a time and then re-obtaining overall estimates. Publication bias among included studies was checked employing Begg’s funnel plot and Egger’s test.ResultsCD152 polymorphism rs231775 decreased cervical cancer risk in total analysis under the genetic models of GG vs. AA, GG vs. AA + AG and G vs. A (OR = 0.73, 95 % CI = 0.59–0.91; OR = 0.78, 95 % CI = 0.65–0.94; OR = 0.92, 95 % CI = 0.87–0.98), and so did the polymorphism rs3087243 in total analysis under the comparisons of AA vs. GG, AA + GA vs. GG, AA vs. GG + GA, A vs. G and GA vs. GG (OR = 0.51, 95 % CI = 0.42–0.60; OR = 0.71, 95 % CI = 0.62–0.82; OR = 0.57, 95 % CI = 0.50–0.66; OR = 0.70, 95 % CI = 0.64–0.77; OR = 0.83, 95 % CI = 0.72–0.97). Besides, the polymorphism rs5742909 elevated the disease onset in total analysis under the contrasts of TT vs. CC, TT + CT vs. CC, TT vs. CC + CT, T vs. C and CT vs. CC (OR = 2.66, 95 % CI = 1.75–4.04; OR = 1.54, 95 % CI = 1.24–1.91; OR = 2.13, 95 % CI = 1.12–4.03; OR = 1.44, 95 % CI = 1.17–1.78; OR = 1.49, 95 % CI = 1.22–1.83).ConclusionCD152 polymorphisms rs231775 and rs3087243 significantly decrease the risk of cervical cancer, while rs5742909 may increase the disease risk.     

Association of CAV1 polymorphisms with the risks of breast cancer: A systematic review and meta-analysis

BackgroundCaveolin-1 (CAV1) polymorphisms have been shown to correlated with breast cancer risk in previous studies. However, the role of CAV1 polymorphisms still remained indecisive, and dual functions of CAV1 was demonstrated in breast cancer development. Consequently, a meta-analysis to evaluate and summarize the association of the CAV1 polymorphisms with breast cancer susceptibility.Material and methodsExtensive search was performed in PubMed, Web of Science, Google scholar, EMBASE.com, CNKI and Wanfang searching platform up to March 2019. The Newcastle–Ottawa Scale (NOS) were used to evaluate the quality of each study. The Odds ratios (ORs) and the 95% confidence intervals (CIs) were analyzed to evaluate the strength of the associations in five genetic models. Inter-study heterogeneity was quantified using the I-squared (I²) test. In addition, the Egger’s test and Begg’s test were applied to evaluate the publication bias.Results4 case-control studies with 2115 cases and 2138 controls were enrolled into this analysis. There was a significant association between rs3807987 polymorphism of CAV1 and breast cancer in allele comparison (A vs. G: OR = 1.288, 95％CI = 1.162–1.428, P < 0.001), heterozygote comparison (AG vs. GG: OR= 1.422, 95％CI=1.233–1.639, P < 0.001), and dominant comparison (AA+AG vs. GG: OR=1.395, 95％CI=1.228-1.586, P < 0.001). A significant association of rs3807987 polymorphism in allele comparison (A vs. G: OR=1.238, 95％CI=1.109–1.383, P < 0.001), heterozygote comparison (AG VS. GG: OR=1.466, 95％CI=1.267–1.697, P < 0.05), and dominant comparison (AA+AG vs. GG: OR=1.384, 95％CI=1.209–1.585, P < 0.001) was also founded amongst Chinese population. A significant association between rs7804372 polymorphism and breast cancer amongst Chinese population in recessive comparison (AA vs. AT + TT: OR = 0.730, 95％CI = 0.567–0.940, P = 0.015) was identified. No significant association between breast cancer risk and rs1997623 was found.ConclusionCAV1 rs3807987 and rs7804372 polymorphisms are associated with the change of breast cancer risk. More well-designed and large studies in various populations are needed to further elaborate these associations.