A novel PCR-based method for direct Fc gamma receptor IIIa (CD16) allotyping

Leukocyte IgG receptors (Fc gamma R) are important immune-response modulating molecules. Fc gamma RIIIa is expressed on macrophages, NK-cells and gamma delta-T cells and exhibits a genetically determined, functional polymorphism at nucleotide 559. This allelic difference predicts either a phenylalanine (F158) or valine (V158) at amino acid 158 in the membrane-proximal extracellular domain, and has been shown to be associated with autoimmune and infectious diseases. Published methods to determine Fc gamma RIIIa genotypes are cumbersome. Therefore, we developed a novel, rapid and reliable PCR-based method to determine Fc gamma RIIIa genotypes. Comparison of genotyping results with direct Fc gamma RIIIa sequencing of 60 blood donors showed 100% accuracy of this new method. Since genotype frequencies of Fc gamma R polymorphisms depend strongly on race and ethnicity, we compared Fc gamma RIIIa genotype frequencies of 176 Caucasian Dutch and 104 Japanese blood donors. Interestingly, these frequencies were not significantly different (P>0.1), in contrast to the Fc gamma RIIa and Fc gamma RIIIb genotype frequencies (P<0.001).     

Association of the leukocyte immunoglobulin G (Fcγ) receptor IIIa-158V/F polymorphism with inflammatory myopathies in Dutch patients

Leukocytes are involved in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Immunoglobulin G (IgG) receptors (FcγR) link the specificity of IgG to the effector functions of leukocytes. Several FcγR subclasses display functional polymorphisms that determine in part the vigour of the inflammatory response. FcγRIIIa genotypes were differentially distributed among 100 IIM patients compared with 514 healthy controls with a significant increase of the homozygous FcγRIIIa-V-158 genotype (3 × 2 contingency table, χ² = 6.3, P  = 0.04). Odds ratios (ORs) increased at the addition of each FcγRIIIa-V-158 allele, in particular among patients with non-specific myositis and dermatomyositis {OR 2.1 [95% confidence interval (CI) 1.1–4.3] and 2.7 (95% CI 1.1–6.4) for FcγRIIIa-V/F158 and FcγRIIIa-V/V158 genotypes, respectively, using FcγRIIIa-F/F158 as a reference group}. These data suggest that the FcγRIIIa-V-158 allele may constitute a genetic risk marker for IIM.     

Interleukin‐17F single‐nucleotide polymorphism (7488T>C) and its association with susceptibility to leprosy

The objective of this study was to investigate the association, if any, between the interleukin‐17F (7488T>C) (rs763780) polymorphism and susceptibility to leprosy and to elucidate the relationship between IL‐17F genotypes and clinical profile of the disease. DNA was extracted from the peripheral venous blood of leprosy cases (n = 140), which were classified as per WHO classification into paucibacillary (PB) (n = 53) and multibacillary (MB) (n = 87) categories and healthy controls (n = 84) without any signs and symptoms of leprosy. The IL‐17F (7488 T/C) polymorphism was genotyped using amplification refractory mutation system – polymerase chain reaction (Allele‐specific amplification). In both PB and MB categories of leprosy cases, the homozygous TT genotype frequency was significantly higher than that of the healthy controls (78.70% vs. 29.76%, P < 0.05). The heterozygous TC genotype was higher in the controls than in the leprosy cases (57.14% vs. 17.68%, P < 0.05). TT genotype was more associated with the type 1 reactional states and tuberculoid/borderline tuberculoid groups in leprosy than the TC genotype. This study reveals that the IL‐17F (7488T>C) single‐nucleotide polymorphism is associated with susceptibility to leprosy and polymorphism confers decrease in risk of contracting leprosy in the north Indian cohort.     

Glutathione S‐Transferase M1 and T1 Gene Polymorphisms and the Outcome of Chronic Hepatitis C Virus Infection in Egyptian Patients

We analysed the distribution of GSTM1 and GSTT1 gene polymorphisms in Egyptian patients with chronic hepatitis C, and investigated their relationship to the clinical outcome of chronic hepatitis C virus (HCV) infection. This study included 169 patients with chronic HCV infection and 145 healthy and matched controls.GSTM1 and GSTT1 polymorphisms were genotyped by multiplex polymerase chain reaction. Individual GSTM1 null and GSTT1 null genotypes were more frequent in patients versus control subjects [OR, 4 (95% CI, 2.5–6.4); P ? 0.001] and [OR, 1.7 (95% CI, 1.1–2.6); P = 0.025], respectively. The patient group showed a higher frequency of the combined GSTM1/GSTT1 double‐null genotype than the control group [OR, 1.8 (95% CI, 1.1–2.9); P = 0.016]. The distribution frequencies of the combined GSTM1/GSTT1 double‐null genotype were significantly different [OR, 0.5 (95% CI, 0.25–0.99); P = 0.049] between F0–F3 and F4. There were no significant differences between the two groups with regard to other genotypes. The combined GSTM1/GSTT1 double‐null genotype was significantly increased in Child‐Pugh C patients in comparison to Child‐Pugh A+B (P = 0.02). There was no significant difference between different classes with regard to other genotypes. In conclusion, we identified an association between the combined GSTM1/GSTT1 double‐null genotype and advanced liver fibrosis and outcome of chronic HCV infection in Egyptian patients.     

Adenosine deaminase alleles and autistic disorder: Case‐control and family‐based association studies

Adenosine deaminase (ADA) plays a relevant role in purine metabolism, immune responses, and peptidase activity, which may be altered in some autistic patients. Codominant ADA1 and ADA2 alleles code for ADA1 and ADA2 allozymes, the most frequent protein isoforms in the general population. Individuals carrying one copy of the ADA2 allele display 15 to 20% lower catalytic activity compared to ADA1 homozygotes. Recent preliminary data suggest that ADA2 alleles may be more frequent among autistic patients than healthy controls. The present study was undertaken to replicate these findings in a new case‐control study, to test for linkage/association using a family‐based design, and to characterize ADA2‐carrying patients by serotonin blood levels, peptiduria, and head circumference. ADA2 alleles were significantly more frequent in 91 Caucasian autistic patients of Italian descent than in 152 unaffected controls (17.6% vs. 7.9%, P = 0.018), as well as among their fathers. Family‐based tests involving these 91 singleton families, as well as 44 additional Caucasian‐American trios, did not support significant linkage/association. However, the observed preferential maternal transmission of ADA2 alleles, if replicated, may point toward linkage disequilibrium between the ADA2 polymorphism and an imprinted gene variant located in its vicinity. Racial and ethnic differences in ADA allelic distributions, together with the low frequency of the ADA2 allele, may pose methodological problems to future linkage/association studies. Direct assessments of ADA catalytic activity in autistic individuals and unaffected siblings carrying ADA1/ADA1 vs ADA1/ADA2 genotypes may provide stronger evidence of ADA2 contributions to autistic disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:784–790, 2000. © 2000 Wiley‐Liss, Inc.     

Associations of the IL‐1F7 gene polymorphisms with rheumatoid arthritis in Chinese Han population

Our aim was to investigate whether genetic polymorphism of IL‐1F7 (rs3811047) was involved in the susceptibility to rheumatoid arthritis (RA) in Chinese Han population. Single nucleotide polymorphism (SNP) of IL‐1F7 gene (rs3811047) was analyzed in 184 unrelated Chinese Han patients with RA and 184 healthy controls by ligase detection reaction based on high temperature ligase detection reactions polymerase chain reaction (LDR‐PCR). There were no statistically significant differences in the genetic polymorphism (genotypes and allele frequencies) of IL‐1F7 (rs3811047) in the patients with RA compared with control. Although all of the clinical and laboratory measures were similar to each other among patients with different genotypes, RA patients carrying AA or AG genotypes had lower swollen joint count, swollen joint index, rest pain and health assessment questionnaire (HAQ) score than that in patients having GG genotype (P < 0.05). These findings show that no evidence for the involvement of a pro‐inflammatory polymorphism in the IL‐1F7 in the susceptibility to RA in China. Patients carrying A allele had less severe disease activity than those not carrying this allele, suggesting that the A allele of IL‐1F7 gene (rs3811047) may have a protective effect on RA.     

Associations between FCGR polymorphisms and immune thrombocytopenia: A meta‐analysis

Several studies already explored associations between Fc gamma receptor (FCGR) polymorphisms and immune thrombocytopenia (ITP), but the results of these studies were not consistent. Consequently, we conducted a meta‐analysis of relevant studies to better analyse the effects of FCGR polymorphisms on individual susceptibility to ITP. PubMed, Web of Science, Embase and CNKI were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Totally 17 studies were eligible for analyses (1200 cases and 1723 controls). Significant associations with ITP were observed for FCGR3A F158V polymorphism in dominant (P < 0.0001, OR = 0.47, 95% CI 0.39‐0.57), recessive (P < 0.0001, OR = 2.03, 95% CI 1.58‐2.61), overdominant (P < 0.0001, OR = 1.42, 95% CI 1.19‐1.69) and allele (P < 0.0001, OR = 0.58, 95% CI 0.51‐0.65) models in overall analyses. But we did not observe any significant associations with ITP for FCGR2A H131R and FCGR2B I232T polymorphisms in overall analyses. Subgroup analyses by ethnicity yielded similar positive results for FCGR3A F158V polymorphism in both Asians and Caucasians. Furthermore, subgroup analyses by type of disease revealed that FCGR2A H131R polymorphism was significantly associated with childhood‐onset ITP, and FCGR3A F158V polymorphism was significantly associated with both childhood‐onset and adult‐onset ITP. In summary, our findings suggested that FCGR2A H131R polymorphism may serve as a potential genetic biomarker of childhood‐onset ITP, while FCGR3A F158V polymorphism may serve as a potential genetic biomarker of both childhood‐onset and adult‐onset ITP.     

ORIGINAL ARTICLE: Transforming Growth Factor‐Beta1 Gene Polymorphisms in Korean Patients with Pre‐eclampsia

Citation Kim SY, Lim JH, Park SY, Yang JH, Kim MY, Kim MH, Ryu HM. Transforming growth factor‐beta1 (TGF‐β1) gene polymorphisms in Korean patients with pre‐eclampsia. Am J Reprod Immunol 2010; 63: 291–298 Problem The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor‐beta1 (TGF‐β1) gene are associated with development of pre‐eclampsia (PE) in Korean women. Method of study We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing. Results The frequencies of the 869CC and combined TC/CC genotypes were higher in patients with PE than in healthy controls. In the PE with intrauterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR‐complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC/CC genotypes were significantly associated with an increased risk of IUGR‐complicated PE compared with the 869TT genotype. The TGF‐β1 c.915G>C polymorphism was not detected in our population. Conclusion Our findings indicate that the TGF‐β1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR‐complicated PE.     

Flow cytometric assay for determination of FcgammaRIIIA-158 V/F polymorphism

A single nucleotide polymorphism (SNP) of the FCGR3A gene results in two allotypes of Fcgamma receptor IIIA (FcgammaRIIIA) with valine (V) or phenylalanine (F) at amino acid 158. Since the FcgammaRIIIA-158 V/F polymorphism is associated with the efficacy of monoclonal antibody (mAb) treatment and a risk factor for autoimmune disease, widely applicable methods to assess the SNP are needed. We developed a novel flow cytometric test for this polymorphism using a mAb that recognized only the FcgammaRIIIA-158 V allele (MEM-154) together with a mAb that detected both FcgammaRIIIA-158 alleles (3G8). The expression of both FcgammaRIIIA epitopes on natural killer (NK) cells from 37 healthy donors were measured and compared to the FCGR3A genotype determined by a 5' nuclease assay. FcgammaRIIIA expression levels in individuals with identical FCGR3A genotypes varied considerably, resulting in overlapping immunofluorescences by both 3G8 and MEM-154 between FcgammaRIIIA-158 V/F allotypes. However, the ratio between fluorescences measured using those mAbs in a single individual predicted the FCGR3A genotype with 100% sensitivity and specificity. The novel flow cytometric assay for the FcgammaRIIIA-158 V/F polymorphism that is based on the MEM-154/3G8 fluorescence ratio requires commercially available reagents and a three-color flow cytometer only.     

HLA‐G gene 14‐bp deletion variant protects Iranian subjects against chronic hepatitis B infection

To investigate whether 14‐bp Ins/Del polymorphism in HLA‐G gene is associated with the risk of chronic hepatitis B (CHB) infection. This study was performed on a total of 396 individuals including 199 CHB patients and 197 healthy subjects from a south‐east Iranian population. We genotyped 14‐bp Ins/Del polymorphism in the HLA‐G gene using polymerase chain reaction method. The results of our study revealed that the HLA‐G 14‐bp deletion polymorphism was associated with a reduced risk of CHB at both allele and genotypic levels. The 14‐bp Del allele and Ins/Del genotype were more frequent in control group than in CHB patients (37% vs 28% for Del allele with OR = 0.68 and p‐value = .015; 73% vs 52% for Ins/Del genotype with OR = 0.43 and p‐value = .001) and both were protective factors against CHB. However, no difference was found in the distribution of HLA‐G 14‐bp genotypes among subjects with varied levels of HBV DNA or hepatic enzymes (p > .05). Our findings, for the first time, suggest that the HLA‐G 14‐bp Ins/Del polymorphism may be a marker for genetic susceptibility to CHB infection.     

Anti‐HIV‐1 antibody‐dependent cellular cytotoxicity mediated by hyperimmune bovine colostrum IgG

Antibodies with antibody‐dependent cellular cytotoxicity (ADCC) activity play an important role in protection against HIV‐1 infection, but generating sufficient amounts of antibodies to study their protective efficacy is difficult. HIV‐specific IgG can be easily and inexpensively produced in large quantities using bovine colostrum. We previously vaccinated cows with HIV‐1 envelope gp140 and elicited high titers of anti‐gp140‐binding IgG in colostrum. In the present study, we determined whether bovine antibodies would also demonstrate specific cytotoxic activity. We found that bovine IgG bind to Fcγ‐receptors (FcγRs) on human neutrophils, monocytes, and NK cells in a dose‐dependent manner. Antibody‐dependent killing was observed in the presence of anti‐HIV‐1 colostrum IgG but not nonimmune colostrum IgG. Killing was dependent on Fc and FcγR interaction since ADDC activity was not seen with F(ab’)₂ fragments. ADCC activity was primarily mediated by CD14⁺ monocytes with FcγRIIa (CD32a) as the major receptor responsible for monocyte‐mediated ADCC in response to bovine IgG. In conclusion, we demonstrate that bovine anti‐HIV colostrum IgG have robust HIV‐1‐specific ADCC activity and therefore offer a useful source of antibodies able to provide a rapid and potent response against HIV‐1 infection. This could assist the development of novel Ab‐mediated approaches for prevention of HIV‐1 transmission.     

No association between alpha‐1‐antichymotrypsin polymorphism and Alzheimer's disease in Koreans

To examine the possible involvement of the alpha‐1‐antichymotrypsin gene (ACT) polymorphism in the manifestation of Alzheimer's disease (AD), we analyzed genotypes of the ACT and apolipoprotein E gene (APOE) among 110 Korean patients with probable AD and 209 nondemented controls. No significant difference was obtained in genotypic (χ²=1.98, df=2, P>0.1) and allelic frequencies (χ²=1.61, df=1, P>0.1) of ACT between the AD and control groups. No overexpression of the ACT A/A genotype and ACT A allele was found when we analyzed the late‐onset AD patients and the early‐onset AD patients, separately. Then we stratified the ACT genotypes based on the presence or absence of the APOE ϵ4 allele to evaluate the possible interaction between them. In the APOE ϵ4‐negative subjects, although the ACT A allele tended to be overexpressed in the AD group, the differences in the frequencies of the ACT A allele (χ²=2.79, df=1, P>0.1) and ACT A/A genotype (χ²=0.16, df=1, P>0.1) were not statistically significant. No significant overrepresentations of the ACT A allele (χ²=0.02, df=1, P>0.1) and ACT A/A genotype (χ²=0.17, df=1, P>0.1) were found in the APOE ϵ4‐positive subjects, either. In addition, the status of the ACT genotype did not influence the age‐at‐onset of AD (F=0.03, df=2, P>0.1). Therefore, the ACT polymorphism does not contribute to the development of AD independently or interactively with the APOE ϵ4 allele in Koreans. Am. J. Med. Genet. 91:355–358, 2000. © 2000 Wiley‐Liss, Inc.     

Interaction Between Val158Met Catechol‐O‐Methyltransferase Polymorphism and Social Cognitive Functioning in Schizophrenia: Pilot Study

The Val158Met catechol‐O‐methyltransferase (COMT) functional polymorphism may influence social cognitive functioning in patients with schizophrenia. Aspects of social cognition were evaluated with the Facial Expression Recognition Test, the Voice Emotion Recognition Test, and the Reading the Mind in the Eyes Test. The Short Recognition Memory Test for Faces was used as a control measure. The Schedule for the Assessment of Negative Symptoms, Schedule for the Assessment of Positive Symptoms, and Beck Depression Inventory were used to rate of patient symptoms. There were 100 patients with the following genotypes: Val/Val (21), Met/Met (30), and Val/Met (49). The genotype distribution of polymorphism of Val158Met COMT did not differ between the patient and control groups. Schizophrenia carriers of the Val/Val genotype performed worse in social cognitive measures, in comparison with the other groups. No statistically significant correlations were recorded between age at schizophrenia onset and polymorphism of Val158Met COMT. There was an influence of genotype in the control group: the Met homozygotes performing better. Schizophrenia patients homozygous for the Val allele showed significant disadvantages over patients homozygous or heterozygous for the Met allele in social cognitive processes. The COMT genotype may not, however, contribute to the age of onset of schizophrenia.     

Fc gamma RIIa, IIIa and IIIb polymorphisms in Turkish children susceptible to recurrent infectious diseases

Abstract The efficacy of IgG-induced Fc gamma receptor (FcγR) function displays interindividual heterogeneity due to genetic polymorphisms of three FcγR subclasses: FcγRIIa, FcγRIIIa and FcγRIIIb. FcγR polymorphisms may contribute to disease susceptibility or may alter disease course. The aim of this study is to examine FcγR gene polymorphisms in Turkish children with recurrent respiratory tract infections and without well known humoral immunodeficiencies. For the patients in the study group (n=52), recurrent infection was defined as the presence of at least six infection episodes a year. Seventy-one healthy children with a maximum of two infections in a year were enrolled as the control group. Subjects in both groups had no abnormalities in serum immunoglobulins, IgG subsets and specific antibody levels. For FcγRIIa: H131H, H131R, R131R genotypes and 131R, 131H alleles; for FcγRIIIa: F158F, F158V, V158V genotypes and 158F, 158V alleles; and for FcγRIIIb: –NA1/NA1, NA1/NA2, NA2/NA2 genotypes and NA1, NA2 alleles were determined by using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Compared with the control group, the FcγRIIa-R131R genotype and 131R allele were found to be significantly elevated in the study group, and FcγRIIa-H131H genotype and 131H allele in the study group were significantly lower than in the control group. Genotypes and alleles related with FcγRIIIa and FcγRIIIb gene polymorphisms did not show any significant difference between the study and control groups. FcγRIIa gene polymorphism (R131R) may increase the risk and susceptibility for recurrent infectious diseases in children.     

Relevance of Fc gamma RIIIa-158V-F polymorphism to recurrence of adult periodontitis in Japanese patients.

The immunoglobulin receptor Fc gamma RIIIa (CD16) is distributed on natural killer (NK) cells, macrophages, and gamma delta T cells, and is polymorphic. Fc gamma RIIIa-158V has a higher affinity for both monomeric and immune complexed IgG1, IgG3, and IgG4 than IIIa-158F. We determined Fc gamma RIIIa-158V/F genotypes of Japanese patients with adult periodontitis. A significant over-representation of Fc gamma RIIIa-158F was found in patients with recurrence, compared with patients without recurrence, making Fc gamma RIIIA a candidate gene for recurrence risk of adult periodontitis.     

Effect of matrix metalloproteinase‐21 (572C/T) polymorphism on HIV‐associated neurocognitive disorder

Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV‐associated neurocognitive disorders (HAND). The coding region polymorphism in MMP‐21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP‐21 polymorphism with the modulation of HAND severity and its prevalence in HIV‐infected and healthy individuals. Genotyping of MMP‐21 572C/T polymorphism was performed by PCR‐RFLP in total 150 HIV‐infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP‐21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP‐21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP‐21 572TT genotype underrepresented in HIV‐infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP‐21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP‐21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP‐21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV‐infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP‐21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP‐21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.     

CD86 +1057G/A polymorphism and risk of chronic immune thrombocytopenia

Abstract

The G to A transition at position +1057 single nucleotide polymorphism site in CD86 gene results in the alanine to threonine substitution, which further affects the antigen-presenting cells' signal transduction. Thus, the purpose of this study was to determine the association between CD86 +1057G/A polymorphism and the risk for chronic immune thrombocytopenia (cITP). The CD86 +1057G/A polymorphism in 158 cITP patients and 150 healthy controls were detected by polymerase chain reaction restriction fragment length polymorphism and then confirmed by DNA sequencing. In the patients with cITP, the frequencies of GG, AG and AA genotypes and G and A alleles were 18.4%, 58.8%, 22.8%, 47.8% and 52.2%, respectively. No difference in genotype and allele frequencies was detected in total cITP patients and normal controls (p?=?0.913 and 0.845, respectively). Cases were subsequently classified by age at diagnosis, gender or clinical responses to glucocorticoids, and still no obvious discrepancy of genotype and allele frequencies was found between each of the groups and normal controls. In conclusion, this study suggests that CD86 +1057G/A polymorphism may be not associated with the genetic susceptibility to cITP in a Chinese population.     

Human leucocyte antigen‐G 14‐bp InDel polymorphism and oral squamous cell carcinoma risk in Chinese Han population: A case–control study

Human leucocyte antigen‐G (HLA‐G) is a nonclassical HLA class I molecule involved in tumour immune escape. The purpose of this study was to investigate the association between the 14‐bp insertion/deletion (InDel) polymorphism in the 3′ untranslated region (3′‐UTR) of HLA‐G gene and oral squamous cell carcinoma (OSCC) risk in Chinese Han population (216 cases and 193 healthy controls), and furthermore, to evaluate serum soluble HLA‐G (sHLA‐G) levels in the OSCC patients. Our results demonstrated that the Ins allele was significantly less frequent in the OSCC patients than that in the healthy controls (odds ratio [OR] = 0.75; 95% confidence interval [CI]: 0.57–0.99; p = 0.040). Distribution of the 14‐bp genotypes in the OSCC patients and the healthy controls revealed that the Ins/Ins genotype was associated with decreased OSCC risk in both the codominant model (Ins/Ins versus Del/Del; OR = 0.57; 95% CI = 0.33–0.99; p = 0.044) and the log‐additive model (OR = 0.76; 95% CI: 0.58–0.99; p = 0.044). The serum sHLA‐G level was significantly higher in the OSCC patients than those in the healthy controls (p < 0.001). Receiver operating characteristic (ROC) curve revealed the valuable diagnostic value of sHLA‐G for OSCC detection, with an area under the ROC curve (AUC) of 0.891 (95% CI: 0.856–0.925, p < 0.001). The OSCC patients with Ins/Ins genotype had lower serum sHLA‐G levels than those with Ins/Del and Del/Del genotypes (p = 0.015). Furthermore, serum sHLA‐G levels were significantly increased with the increasing TNM stages of the OSCC patients (p = 0.017). Our findings revealed that the HLA‐G 14‐bp InDel polymorphism might be a genetic risk factor for OSCC susceptibility, and the serum sHLA‐G may act as a promising biomarker for noninvasive diagnosis of OSCC.     

Association of rheumatoid factor production with FcgammaRIIIa polymorphism in Taiwanese rheumatoid arthritis

Fcgamma receptors (FcgammaR) impact upon the development of inflammatory arthritis through immune complex stimulation and proinflammatory cytokine production. FcgammaRIIa, FcgammaRIotaIotaIotaa and FcRgammaIIIb polymorphisms were genotyped in 212 rheumatoid arthritis (RA) patients and 371 healthy control subjects using an allelic-specific polymerase chain reaction (PCR). No significant skewing in the distribution of FcgammaRIIa H/R131, FcgammaRIIIa F/V158 and FcgammaRIIIb NA1/NA2 was found between RA patients and healthy control subjects. However, a significant skewing distribution of the FcgammaRIIIa F/V158 polymorphism was observed between rheumatoid factor (RF)-positive versus RF-negative RA patients (P = 0.01). The low-affinity FcgammaRIIIa F158 allele seems to have a protective role in RF production, in comparison with the FcgammaRIIIa V158 allele (P = 0.004; OR = 0.485; 95% CI: 0.293-0.803). A high frequency of FcgammaRIIIa F/F158 was identified in RA patients with negative RF compared with RF-positive patients (for FF158 versus FV158 + VV158; P = 0.002; OR = 0.372; 95% CI: 0.194-0.713). In addition, no association was found between FcgammaRIIa H/R131, FcgammaRhoIIIa F/V158 and FcgammaRIIIb NA1/NA2 polymorphisms and other clinical parameters. The results of this study suggest that three activating FcgammaRs polymorphisms lack association with RA but FcgammaIIIa F/V158 polymorphism may influence RF production and IgG RF immune complex handling in Taiwanese RA patients.