Semaphorin-3A,semaphorin-7A gene single nucleotide polymorphisms,and systemic lupus erythematosus susceptibility

Abstract

Background: Semaphorin-3A (Sema3A) and Semaphorin-7A (Sema7A) play crucial roles in immune system by inhibiting T cell proliferation and leading to the secretion of pro-inflammatory cytokines. Increasing evidence suggest that Sema3A and Sema7A may link to the development and pathogenesis of systemic lupus erythematosus (SLE).

Objective: This study aims to evaluate the association of Sema3A, Sema7A gene single-nucleotide polymorphisms (SNPs) with susceptibility to SLE.

Methods: There were 495 SLE patients and 493 healthy controls in the study. Sema3A gene and Sema7A gene were genotyped by improved multiple ligase detection reaction (iMLDR), their plasma expression levels were detected by enzyme-linked immunosorbent assay (ELISA).

Results: No differences in genotype and allele frequencies of these SNPs were observed between SLE patients and healthy controls. However, analysing Sema3A and Sema7A SNPs with clinical manifestations of SLE indicated that, in Sema3A, the A allele frequencies of rs7804122 polymorphism was higher in patients with oral ulcers. In Sema7A, there were differences in allele frequencies of the rs2075589 and rs28362930 polymorphisms between SLE patients with haematological disorder and those without. The GG genotype and G allele frequencies of rs28362930 and the CC genotype, and C allele frequencies of rs741761 were both related to discoid rash in SLE patients. The allele frequency of G (rs28362930) was higher in SLE patients with renal disorder. There were differences in the genotype frequencies and allele frequencies of rs741761 between SLE patients with and without arthritis. No differences in plasma Sema3A and Sema7A levels were detected in SLE patients of different genotypes.

Conclusions: Sema3A and Sema7A gene polymorphisms are not related to SLE genetic susceptibility, but may link to several clinical features of SLE.     

Analysis of CD28 and CTLA-4 gene polymorphisms in Turkish patients with Behcet's disease

In this study we aimed to investigate IVS3 +17T/C single nucleotide polymorphism (SNP) of CD28 gene, +49A/G and ?318C/T SNPs of CTLA‐4 gene in patients with Behçet's disease (BD) and their potential association to the main clinical features of the disease. These polymorphisms were investigated in a Turkish population of 123 patients with BD and 179 healthy controls, by using PCR‐RFLP technique. HLA‐B*51 genotype was also studied in both groups by using PCR‐SSP. The frequency of IVS3 +17TC genotype of the CD28 gene was significantly increased in BD patients compared to controls (43.6% vs. 31.2%, OR = 1.663, 95% CI = 1.033–2.679, P = 0.039). CTLA‐4 +49GG genotype frequency was found to be significantly lower in patients with BD than those of healthy controls (4% vs. 10.6%, OR = 0.357, 95% CI = 0.130–0.983, P = 0.05). Genotype and allele frequencies of the CTLA‐4–318C/T polymorphism between the BD and healthy control groups were not significantly different (12.2% vs. 10.6%, OR = 1.170, 95% CI = 0.570–2.402, P = 0.713). There were no associations between the studied polymorphisms and the main clinical features of BD. The frequencies of HLA‐B*51 were 60.3% and 30.7% in BD and control groups, respectively (OR = 3.429, 95% CI = 2.115–5.559, P = 0.0001). Association between HLA‐B*51 and each studied polymorphism did not reach to significant levels (OR = 0.479, 95% CI = 0.228–1.004, P = 0.064 for CD28 IVS3 +17TT genotype; OR = 2.180, 95% CI = 1.025–4.639, P = 0.061 for TC genotype; OR = 1.570, 95% CI = 0.870–2.836, P = 0.146 for C allele). These results may suggest that CD28 IVS3 +17TC genotype may be a risk factor for the development of BD, on the contrary CTLA‐4 +49GG genotype may be protective in the studied Turkish population.     

Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a South Korean population

Yoon JH, Park JK, Kang YH, Park YK, Nam SW, Lee JY, Park WS. Lysyl oxidase G473A polymorphism is closely associated with susceptibility to gastric cancer in a South Korean population. APMIS 2011; 119: 762–8. The aim of this study was to determine whether a single nucleotide polymorphism at G473A (rs1800449) within the LOX‐propeptide is associated with susceptibility to gastric cancer. We investigated the genotype and allele frequencies of this gene in tissue specimens from 458 gastric cancer patients and 282 healthy individuals. Polymorphism analysis was performed by amplifying the propeptide region of LOX and digestion with NotI followed by sequencing of the products. The frequencies of the LOX G473A G/G, G/A, and A/A genotypes were 54.4% (249/458), 34.3% (157/458), and 11.3% (52/458), respectively, in gastric cancer patients and 58.9% (166/300), 35.5% (100/282), and 5.7% (16/282), respectively, in the healthy controls. Statistically significant differences in the genotype and allele frequency of LOX rs1800449 were observed between the healthy controls and gastric cancer patients (p = 0.0294 and p = 0.0339). When the data were stratified according to gastric cancer histologic subtype, the risk of diffuse‐type gastric cancer in carriers with an A allele (G/A or A/A genotypes) was statistically higher compared to that of carriers with the G/G genotype (p = 0.0001). Our findings suggest that G473A polymorphism of the LOX gene may be closely associated with susceptibility to the development and differentiation of gastric cancer in South Korean patients.     

Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis

Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (?2578C/A, ?1154G/A, ?460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay in 174 adenomyosis patients and 199 frequency‐matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the ?2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42–0.97]. For the ?1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33–0.80). However, the genotype distributions and allele frequencies of the ?460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF ?460/?1154/?2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41–1.00; OR = 0.44, 95% CI = 0.21–0.93, respectively). The study indicated that the ?2578A or ?1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development. Environ. Mol. Mutagen., 2009. © 2009 Wiley‐Liss, Inc.     

Association of MCP-1 promotor polymorphism with disease severity of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a thick-borne viral zoonotic disease. The pathogenesis and the reasons why cases have a mild or severe course in CCHF have not yet been explained. In this study, we investigated the relationship between promoter -2518 A/G single-nucleotide polymorphism (SNP) of the MCP-1 gene and the clinical course of CCHF. The MCP-1-2518 A/G SNP (rs1024611) frequency was examined in 128 virologically/serologically confirmed CCHF patients and 181 healthy controls by using the PCR-RFLP method. When CCHF patients and controls were compared, no significant difference was found between genotype distributions and allele frequencies of the -2518 A/G SNP of MCP-1 gene (P > .05). Compared to the AA genotype, both AG (P = .016; OR = 2.57) and GG genotype (P = .039; OR = 3.43) were found with significantly higher frequencies in mild/moderate cases than in severe cases. Compared to the AG + GG genotype, AA showed a significant risk for severe CCHF (60.0% vs 38.4%, P = .02; OR = 2.41). In contrast, the AG genotype showed a significant protective effect against severe disease compared to AA + GG genotype (29.1% vs 47.9%, P = .013; OR = 2.58). Compared to mild/moderate cases, the A allele was found to be significantly higher in severe cases (0.745 vs 0.623, P = .039; OR = 1.77). However, no significant relationship was found between fatal and nonfatal cases in terms of genotype or allele frequencies (P > .05). In conclusion, both -2518 AA genotype and A allele of MCP-1 were associated with disease severity, and the AG genotype had a protective effect against a severe disease course in CCHF patients.     

Gene Polymorphism of Interleukin-4, Interleukin-4 Receptor and STAT6 in Children with Atopic Dermatitis in Taif,Saudi Arabia

Aim of study: This work was performed to evaluate the level of IL-4, and to clarify the role of IL-4 gene polymorphism at position cytosine –590-to-thyamine (C-590T), IL-4Rα gene polymorphism at position adenine +4679-to-guanine (A+4679G) [isoleucine-50-valine (I50V)] and STAT6 gene polymorphism at position guanine 2964-to-adenine (G2964A) in Saudi children with non-atopic dermatitis (non-AD) and atopic dermatitis (AD) to identify their role in the pathogenesis of these diseases.

Subjects and methods: This study included 150 children: 50 healthy children as controls, 50 with non-AD, and 50 with AD. They were subjected to full clinical examination, complete blood picture, skin prick test, and determination of serum interleukin-4 (IL-4) and total immunoglobulin-E (IgE) levels. Detection of interleukin-4 gene (C-590T), interleukin-4 receptor alpha gene (A+4679G) (I50V), and STAT6 gene (G2964A) polymorphisms were performed by PCR-based restriction fragment length polymorphism (PCR-RFLP).

Results: There was a significant (P < 0.01) association between genotype and allele frequencies of IL-4Rα (A+4679G) (I50V) polymorphism in the AD group (but not non-AD group). Moreover, there was a significant association between genotype and allele frequencies of the STAT6 (G2946A) polymorphism in the non-AD (P < 0.05) and AD (P < 0.01) groups. On the other hand, there was no significant association between genotype and allele frequencies of the (C-590T) polymorphism in the non-AD group and AD group. There was a significant (P < 0.001) higher total IgE level in patients compared to the controls. Moreover, the mean values of total IgE were significantly different among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively, in all the studied groups. On the other hand, there was no significant difference of serum IL-4 levels among all the studied patients, or among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively.

Conclusion: IL-4Rα gene (I50V) and STAT6 gene (G2964) polymorphisms may play a role in development of eczema; however, the IL-4 gene polymorphism (C-590T) had no relationship with susceptibility to the disease among Saudi children.     

Association of CD1A +622 T/C, +737 G/C and CD1E +6129 A/G Genes Polymorphisms with Multiple Sclerosis

Antibodies and specific T cells to glycolipids have been found in MS patients. CD1 molecules are involved in presentation of lipid antigens to T-cells. Therefore, functional polymorphisms in two CD1 genes (+622 T/C and +737 G/C in CD1A along with +6129 A/G in CD1E) might be associated with susceptibility to MS. First, 351 MS patients and 342 controls were enrolled in this study. Allele-specific oligonucleotide polymerase chain reaction and PCR-RFLP methods were used for genotyping. The frequency of CD1A genotypes was not different between cases and controls. However, investigating females, the frequency of CD1A*01 allele was significantly higher in patients with PP-MS compared to controls (p = 0.028) as well as to RR-MS and SP-MS (p = 0.042 and 0.021, respectively). The distribution of CD1E +6129 A allele (CD1E*01) and CD1E*01/01 genotype is more frequent in normal controls in comparison with MS patients (p = 0.001 and p = 0.0003, respectively). In addition, after categorization of study groups according to disease types, differences between alleles and genotypes of CD1E gene polymorphism remained significant for RR-MS patients compared to those of normal controls (p = 0.0001 and p = 0.0003, respectively). CD1E and CD1A genes may be involved in networks which determine susceptibility to RR-MS and PP-MS, respectively.     

Association of Crohn’s Disease with Aryl Hydrocarbon Receptor Gene Polymorphisms in Patients from Southeast China

ABSTRACT

Aims The aryl hydrocarbon receptor (AhR) plays a pivotal role in regulating the innate and the acquired immune systems. The present study aimed to investigate the association of Crohn’s disease (CD) with AhR polymorphisms in a cohort of patients from Southeast China.

Methods An improved multiple ligase detection reaction technique was applied to examine the polymorphisms of rs2158041, rs2066853, and rs10249788 in 310 patients with CD and 573 controls.

Results Compared to the controls, the variant allele (T) and genotype (CT+TT) of rs2158041 were less frequent in patients with CD (both p < 0.05). Similar conclusions were drawn from patients with ileal CD and with stricture CD as compared to the controls (all p < 0.0083). However, no significant differences were observed in allele and genotype frequencies of rs2066853 and rs10249788 between patients with CD and the controls (all p > 0.05). Although rs2158041 and rs10249788 were in complete linkage disequilibrium with rs2066853, respectively, only the frequency of haplotype (TG) formed by rs2158041 and rs2066853 was significantly lower in patients with CD than that in the controls (p < 0.05).

Conclusions AhR (rs2158041) might be a susceptible locus for CD, especially for the two subtypes: ileal CD and stricture CD.     

Association of SOD1 and SOD2 single nucleotide polymorphisms with susceptibility to gastric cancer in a Korean population

Oxidative stress is accepted as one of the main factors involved in the development and progression of cancer. Superoxide dismutases (SODs) are important in avoiding oxidative stress by eliminating reactive oxygen species (ROS). To determine whether single nucleotide polymorphisms at G7958A within SOD1 and at T5482C within SOD2 are associated with an increased susceptibility to gastric cancer, we investigated the genotype and allele frequencies of the genes from 294 gastric cancer patients and 300 healthy individuals. A polymerase chain reaction‐single strand conformation polymorphism assay was used to identify the SOD1 G7958A and the SOD2 T5482C genotypes. Statistically significant differences in the genotype and allele frequencies of SOD2 T5482C were found between the healthy controls and gastric cancer patients (p = 0.0001 and p < 0.0001, respectively). When the data were stratified according to gastric cancer histological subtypes, the risk of both diffuse‐ and intestinal‐type gastric cancer was statistically higher for carriers of the C allele compared with carriers of the T allele. However, there were no statistically significant differences in genotype distribution (p = 0.5069) and allele frequencies (p = 0.3714) of SOD1 G7958A between gastric cancer patients and controls. Our findings suggest that polymorphism of the SOD2 T5482C may be closely associated with an increased susceptibility to the development and differentiation of gastric cancer in the Korean population.     

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (?1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (?1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25–9.45; p = 0.014) or 2.35 (1.05–5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.     

Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.     

Association of CTLA4 exon-1 polymorphism with the tumor necrosis factor-α in the risk of systemic lupus erythematosus among South Indians

Cytotoxic T lymphocyte associated-antigen (CTLA4) is a potential negative regulatory molecule of T-cells and associated with several autoimmune diseases. Several reports from different ethnic groups showed that the polymorphisms of the CTLA4 gene have been associated with autoimmune diseases including SLE. Therefore, we aimed to investigate the +49 A/G polymorphism in South Indian SLE patients and its association with disease aetiology and serological markers. A total of 534 samples were genotyped for the +49 A/G polymorphism in exon 1 of the CTLA-4 gene through PCR-RFLP method. We found significant association of genotype and allele frequencies with +49 A/G polymorphism in SLE patients. The frequency of the +49 A/G polymorphism rs231775 ‘GG’ genotype was significantly higher in patients with SLE (12.32%) than those in healthy control subjects (4.6%) (OR: 1.797; 95% CI 1.264–2.554; p = 0.001). The frequency of mutant allele ‘G’ also found to be significantly higher in cases (36.01%) than controls (24.92%) (OR: 1.695, 95% CI: 1.298–2.214, p < 0.001). We observed significant increase in serum TNF-α, interferon-α, IL-10 and IL-12 in SLE cases compared to controls. We also found a significant association of serum TNF-α, interferon-α, IL-10 and IL-12 with SLE phenotypes. In addition there was a significant increase in serum TNF-α level in “GG” genotype SLE subjects suggesting that it might play a major role in the advancement of SLE disease.     

TNF-α-238G/A基因多态性与原发性肝癌的关系

目的 探讨肿瘤坏死因子-α（TNF-α）基因启动子-238G/A多态性与原发性肝癌（PHC）的相关关系.方法 应用聚合酶链反应-限制性片段长度多态性法（PCR-RFLP）检测100例PHC患者和150例健康对照者TNF-α基因启动子-238G/A多态性.结果 TNF-α-238基因型GG、GA频率在PHC组和对照组分别为95.3%和4.7%,88%和12%;等位基因G、A频率在PHC组和对照组分别为97.7%和4.7%,94%和6%.两组差异均有显著性（P＜0.05）,携带GA基因型个体患PHC的风险约是GG基因型的2.786倍（OR=2.786,95%CI=1.057～7.343）.结论 TNF-α-238G/A基因多态性与PHC的发病有相关性,A等位基因可能是PHC的遗传易感基因.     

A polymorphism in the promoter region of the CD86 (B7.2) gene is associated with systemic sclerosis

Systemic sclerosis (SSc) is a connective tissue disease of unknown aetiology characterized by fibrosis of the skin and internal organs, vascular abnormalities and humoral autoimmunity. Strong T‐cell‐dependent autoantibody and HLA associations are found in SSc subsets. The co‐stimulatory molecule, CD86, expressed by antigen‐presenting cells, plays a crucial role in priming naïve lymphocytes. We hypothesized that SSc, or one of the disease subsets, could be associated with single‐nucleotide polymorphisms of the CD86 gene. Using sequence specific primer‐polymerase chain reaction (SSP‐PCR) methodology, we assessed four CD86 polymorphisms in 221 patients with SSc and 227 healthy control subjects from the UK. Haplotypes were constructed by inference and confirmed using PHASE algorithm. We found a strong association between SSc and a specific haplotype (haplotype 5), which was more prevalent in patients than in controls (29% vs 15%, OR = 2.3, χ² = 12, P = 0.0005). This association could be attributed to the novel ?3479 promoter polymorphism; a significant difference was observed in the distribution of the CD86 ?3479 G allele in patients with SSc compared to controls (43.7% vs. 32.4%, OR = 1.7, χ² = 12.1, P = 0.0005). TRANSFAC analyses suggest that the CD86‐3479T allele contains putative GATA and TBP sites, whereas G allele does not. We assessed the relative DNA protein‐binding activity of the ?3479 polymorphism in vitro using electromobility gel shift assays (EMSA), which showed that the ?3479G allele has less binding affinity compared to the T allele for nuclear proteins. These findings highlight the importance of co‐stimulatory pathways in SSc pathogenesis.     

Association of the brain-derived neurotrophic factor gene G196A rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia

This study aimed to explore the association between BDNF G196A gene rs6265 polymorphisms and the cognitive function and clinical symptoms of schizophrenia. Methods: BDNF G196A rs6265 genotype and allele frequency were measured using Polymerase Chain Reaction (PCR) methods in 224 drug-free patients with schizophrenia and 220 controls. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive functioning was assessed using the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT). In the patient group, differences in severity of symptoms across the three genotypes (i.e., G/G, G/A and A/A) of G196A were assessed using one-way analysis of variance. Results G/A genotype had higher frequencies than GG or AA genotype in both patients and controls. There was no significant difference in G/G, G/A, A/A genotype frequency between patients and controls (P > 0.05). The allele G had higher frequencies than allele A in both patients and controls. There was no significant difference in G or A allele frequency between patients and controls (P > 0.05). There was significant difference in A/A genotype frequency between positive group patients and negative group patients. There was no significant difference in cognitive performance between patients with G/G, G/A and A/A genotype (all P > 0.05). Conclusion BDNF G196A gene rs6265 polymorphism is not associated with the cognitive function but with the clinical symptoms of schizophrenia.     

Solute Carrier Family 11 Member A1 Gene Polymorphisms in Reactive Arthritis

To investigate the role of SLC 11A1 polymorphisms in the development of reactive arthritis, 91 patients with reactive arthritis and 163 healthy controls were enrolled in this study. The SLC 11A1 polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. The genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were significantly different between the patients with reactive arthritis and controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the SLC 11A1 274C/T showed a significant association with reactive arthritis. The patients with reactive arthritis have a significantly higher frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was resistant to the development of reactive arthritis. The allele frequencies of SLC 11A1 274T and 823C were significantly increased in the patients with reactive arthritis in comparison with those of the controls, independent of HLA-B27. On the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly decreased in the patients with reactive arthritis. The estimated haplotype frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are associated with susceptibility to reactive arthritis independently of HLA-B27 in Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1 274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.     

Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population

A number of genetic loci have been proposed to be associated with persistent hepatitis B virus (HBV) infection. This study aimed to evaluate the association and interaction of susceptible genes with HBV persistence in a Chinese population. A total of 17 polymorphisms in 9 candidate genes were studied in 361 Chinese chronic hepatitis B patients and 304 patients who recovered spontaneously. Distributions of susceptible polymorphisms were examined in healthy Chinese and Caucasian populations. Gene–gene interactions were tested by the multifactor dimensionality reduction (MDR) method. The TNF ?308 G/G genotype and G allele, IL‐10RB codon 47 A allele, and MCP‐1 ?2518 G/G genotype and G allele were more frequent in patients than controls (P < 0.01, after multiple corrections Pc < 0.05), while the frequencies of TNF ?308 A/G genotype and IL‐10 ?592 A/A genotype were significantly higher in controls than in the patient group (Pc < 0.05). The frequencies of the risk allele MCP‐1 ?2518 G and CTLA4 6230 G were much higher in Chinese than in the Caucasian groups (P < 0.001). An interaction between CCR5 ?2459, TNFA ?863, IL‐10RB codon 47, and MCP‐1 ?2518 was detected by MDR (P = 0.001). The results indicate that genetic determinants may affect the outcome of HBV infection in both independent and synergic manners. J. Med. Virol. 82:371–378, 2010. © 2010 Wiley‐Liss, Inc.     

Association study of interleukin-19 rs2243188 polymorphism with systemic lupus erythematosus in a Chinese population

Abstract

The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP), rs2243188 of interleukin-19 (IL-19), show significant evidence for association with SLE in a Chinese population. A total of 545 SLE patients and 613 healthy controls were collected in the present study. The genotyping of IL-19 rs2243188 polymorphism was detected by TaqMan allele discrimination assay on the 7300 real time polymorphism chain reaction system. The minor C allele of rs2243188, relative to the major A allele, appeared to have a significantly lower frequency in SLE patients (31.0%) as compared with controls (35.5%) (χ²?=?5.19, p?=?0.023). We also discovered a statistical significance in the dominant model (CC?+?CA versus AA: OR?=?0.755, 95% CI?=?0.598–0.953, p?=?0.018). However, no significant difference in genotype distribution was found between SLE patients and controls (p?=?0.056). Furthermore, an increased frequency of CC genotype were also detected in lupus nephritis (LN) groups as compared with non-LN groups (p?=?0.024). Besides, the individuals with CC genotype had a 2.201-fold higher risk for the susceptibility to LN than those A allele carriers (AA?+?CA) (p?=?0.006). Unfortunately, the analyses on the relationship of IL-19 rs2243188 with several clinical manifestations of SLE failed to find any significant results. In conclusion, our observations suggested the minor C allele of SNP rs2243188 might be a protective factor for SLE in a Chinese Han population. Moreover, the subgroup analysis highlighted that IL-19 rs2243188 SNP was associated with the susceptibility to LN patients.     

CTLA‐4 gene polymorphism of exon 1(+49 A/G) in Turkish systemic lupus erythematosus patients

Cytotoxic T lymphocyte‐associated antigen‐4 is a cell‐surface molecule providing a negative signal for T cell activation. CTLA‐4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA‐4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA‐4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27–5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99–3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non‐AA (39.2 ± 11.5 vs. 31.6 ± 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA‐4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA‐4 +49.     

Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women

Citation Xing X, Yan J, Zhao Y, You L, Bian Y, Chen Z‐J. Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women. Am J Reprod Immunol 2011; 65: 521–525 Problem An association of polymorphism ?1154G/A (rs1570360) in vascular endothelial growth factor (VEGF) gene with idiopathic recurrent spontaneous abortion (RSA) has been found in Caucasians. The aim of this study was to examine the association of VEGF ?1154 with RSA in a well‐defined group of Chinese Han patients. Method of study The VEGF ?1154G/A genotype was detected by real‐time PCR with TaqMan probes. The products were also subjected to gene sequence analysis to validate the PCR results. Results The allele frequencies of VEGF ?1154G/A showed no significant difference between RSA patients and the normal controls (P = 0.183). The frequencies of VEGF ?1154G/A genotypes were not significantly different between RSA patients and the normal controls (P = 0.228). Conclusion Our study revealed that VEGF ?1154G/A polymorphism was not associated with the susceptibility to RSA in Chinese Han women.