TAP1 Gene Polymorphisms Research Articles

Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study.

BackgroundRecurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor‐related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP.MethodsA case–control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real‐time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program.ResultsHPV‐6 and HPV‐11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994–7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele.ConclusionThe G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.

Association Tap1 and Tap2 gene polymorphisms with Echinococcosis in Man and Camels (Camelus dromedaries).

Association Tap1 and Tap2 gene polymorphisms with Echinococcosis in Man and Camels (Camelus dromedaries).

TAP1 Gene Polymorphism in Alopecia Areata

Alopecia areata (aa) is a common type of hair loss. It is an autoimmune disease with a variable, typically relapsing or remitting, course that can be persistent-especially when hair loss is extensive. Three major phenotypic variants of the disease are patchy-type aa, alopecia universalis and alopecia totalis. The aim of the present study was to assess the relation between TAP1(rs1057141) gene polymorphism and alopecia areata risk and its clinical criteria. This study was carried out on 100 patients suffering from Alopecia Areata and 100 apparently healthy individuals of matched age and sex as a control group. Patients were recruited from the outpatient clinic of Dermatology and Andrology Department of Benha University Hospitals during the period from August 2018 to January 2019. There was insignificant difference in TAP1 (rs1057141) genotypes in both studied groups. TAP1 (rs1057141) gene polymorphism does not have a role in alopecia areata development.

Association of TAP1 Gene Polymorphism in Human Papilloma Virus Related Oropharyngeal Cancer

Background: Polymorphisms of TAP1 gene might be pertinent in development of cancer by altering the immune response. We studied the association of TAP1 gene polymorphism with HPV related oropharyngeal cancer. Methods: This prospective study consisted of 200 subjects divided into three groups; Group A—HPV positive oropharyngeal cancer (17/100), Group B—HPV negative oropharyngeal cancer (83/100) and Group C—Controls. TAP1ile333val polymorphism genotyping was performed by ARMS-PCR. Results: No significant difference was observed in the distribution of Val/Val genotype of Group A in comparison to Group C (OR = 0.663, 95% CI = 0.164 - 2.688, p = 0.742) and Group B (OR = 1.725, 95% CI = 0.388 - 7.675, p = 0.677) and thus was not associated with HPV associated cancer. But the frequency of Val/Val genotype was found to be significantly decreased in Group B as compared to controls and was linked with increased risk of oropharyngeal cancers (OR = 0.38, 95% CI = 0.15 - 0.97, p = 0.048). Conclusion: TAP1i333v gene polymorphism was not associated with HPV positive oropharyngeal cancer; however decreased frequency of Val/Val genotype raises the risk of oropharyngeal cancer.

Quantitative assessment of the association between TAP2 rs241447 polymorphism and cancer risk.

The findings regarding the relation of transporter associated with antigen processing (TAP) to cancer risk have been inconsistent. The aim of this study was to comprehensively evaluate the association between TAP2 rs241447 polymorphism and cancer susceptibility. A meta-analysis of nine investigations with 2800 cases and 1620 controls was conducted to gain a better understanding of the effect of TAP2 rs241447 polymorphism on cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the correlation between TAP2 gene polymorphism and cancer susceptibility. The pooled results from TAP2 rs241447 polymorphism showed a decreased risk of cancer in two dominant genetic models (GG + AG vs AA: OR = 0.86, 95% CI, 0.75-0.99; AG vs AA: OR = 0.85, 95% CI, 0.73-0.99). From the subgroup analysis, decreased cancer susceptibility was found in Caucasians (GG + AG vs AA: OR = 0.82, 95% CI, 0.68-0.99), especially among the subgroup of cervical carcinoma (GG + AG vs AA: OR = 0.82, 95% CI, 0.69-0.96; AG vs AA: OR = 0.83, 95% CI, 0.70-0.99). Overall, the results suggest that TAP2 rs241447 polymorphism contributes to decreased cancer susceptibility.

Menstrual Blood Human Papillomavirus DNA and TAP1 Gene Polymorphisms as Potential Biomarkers for Screening and Monitoring of Cervical Squamous Intraepithelial Lesion.

Human papillomavirus (HPV) is a known causative factor in the etiology of cervical cancer. HPV DNA genotyping was performed in menstrual blood (MB) collected in napkins from patients with cervical intraepithelial neoplasia (CIN), HPV infection and sexually active apparently normal subjects. In the same patient cohort, MB TAP1 I333V and TAP1 D637G gene polymorphisms were examined. The sensitivity, specificity, and positive and negative predictive values of HPV DNA in the detection of CIN or HPV infection were 83% (223 of 268), 98% (131 of 134), 99% (223 of 226), and 74% (131 of 176), respectively. Moreover, HPV DNA was found in 24% (28/118) patients who had loop electrosurgical excision procedure treatment and 0% (0/76) HPV infected or CIN1 patient with proven recovery. On the other hand, the risk of developing high-grade CIN was significantly reduced for AG and GG genotypes compared with AA genotype and for carriers with a G allele compared with those with an A allele for both polymorphisms. MB HPV DNA is a potential noninvasive marker for screening and monitoring of squamous intraepithelial lesion. Together with TAP1 I333V and TAP1 D637G gene polymorphisms, the combined test may be useful for stratifying high-risk patients for better follow-up strategies.

The influence of TAP1 and TAP2 gene polymorphisms on TAP function and its inhibition by viral immune evasion proteins

Herpesviruses encode numerous immune evasion molecules that interfere with the immune system, particularly with certain stages in the MHC class I antigen presentation pathway. In this pathway, the transporter associated with antigen processing (TAP) is a frequent target of viral immune evasion strategies. This ER-resident transporter is composed of the proteins TAP1 and TAP2, and plays a crucial role in the loading of viral peptides onto MHC class I molecules. Several variants of TAP1 and TAP2 occur in the human population, some of which are linked to autoimmune disorders and susceptibility to infections. Here, we assessed the influence of naturally occurring TAP variants on peptide transport and MHC class I expression. In addition, we tested the inhibitory capacity of three viral immune evasion proteins, the TAP inhibitors US6 from human cytomegalovirus, ICP47 from herpes simplex virus type 1 and BNLF2a from Epstein-Barr virus, for a series of TAP1 and TAP2 variants. Our results suggest that these TAP polymorphisms have no or limited effect on peptide transport or MHC class I expression. Furthermore, our study indicates that the herpesvirus-encoded TAP inhibitors target a broad spectrum of TAP variants; inhibition of TAP is not affected by the naturally occurring polymorphisms of TAP tested in this study. Our findings suggest that the long-term coevolution of herpesviruses and their host did not result in selection of inhibitor-resistant TAP variants in the human population.

The association of LMP7 and TAP2 gene polymorphisms with treatment response to interferon/ribavirin in patients with genotype 1 chronic hepatitis C.

Previous studies have highlighted the important role of genes related to antigen presentation in the spontaneous clearance of hepatitisCvirus. The present study aimed to explore the association between TAP, LMP and tapasin gene polymorphism and treatment response in chronic hepatitisC virus(CHC) patients. Six single nucleotide polymorphisms in TAP, LMP and tapasin genes were genotyped among 352Chinese genotype1 CHC patients with pegylated interferon-α and ribavirin (pegIFN-α/RBV) treatment. There were 232cases achieving sustained virological response(SVR), which yielded an SVR rate of 65.9%. LMP7 rs2071543 variant genotypes [additive model: odds ratio (OR),0.52; 95%confidence interval (CI), 0.33-0.82; P=0.005] and TAP2 rs1800454 variant genotypes (additive model: OR, 0.66; 95%CI, 0.45‑0.98; P=0.039) were suggested to decrease the possibility of achieving an SVR. After conducting combined effect analysis of rs2071543 and rs1800454, the authors found that the SVR rate was lower among patients carrying more unfavorable rs1800454-A and rs2071543-Aalleles, and the SVR rate of carrying 3-4alleles was20%. In addition, carrying two unfavorable alleles led to significantly decreased possibility for SVR (OR, 0.30; 95%CI,0.14-0.61; P=0.001). Multivariate stepwise analysis indicated that rs2071543, rs1800454, glucose, α-fetoprotein, platelets and baseline viral load were risk factors of SVR that were independent of each other. The area under the curve(AUC) consisting of all the above factors produced an AUC of 0.704 (95%CI, 0.647‑0.761; P<0.001). The line charts indicated that the drop in viral load was significantly faster in GGpatients than in GC/CC patients during the whole therapy, which was in accordance with the decline of viral load in rs2071543. The present study illustrated that the carriage of LMP7 rs2071543-AA and TAP2 rs1800454-AA had a negative effect on treatment response to pegIFN-α/RBV among genotype1 patient with CHC in a Chinese Han population.

LOW MOLECULAR MASS POLYPEPTIDE AND TRANSPORTER ANTIGEN PEPTIDE GENES POLYMORPHISM AS THE RISK FACTORS OF CERVICAL CANCER WHICH CAUSED BY HUMAN PAPILLOMAVIRUS TYPE-16 INFECTION IN BALI

Background: Until recently, cervical cancer is one of the major problem in women’s health issue related to its high incidence and mortality rate. The etiology of cervical cancer is the high risk oncogenic group of Human Papillomavirus (HPV), especially HPV-16 and 18 and its phylogenies. Meanwhile in Bali, more than 50% of infection are caused by HPV-16 infection. The main objective of this study was to investigate the role of LMP-2, LMP-7, TAP-1 and TAP-2 gene polymorphism as the risk factor in the cervical cancer carcinogenesis that is caused by HPV-16 infection. Method: A nested non-paired case-control study was conducted at Obstetric and Gynecologic Department Sanglah General Hospital, Bali Indonesia from March 1 until August 31, 2013. Laboratory testing was carried out at Laboratory of Histopathology Leiden University Medical Centre, Netherlands,. Results: A total of 40 samples were collected, consist of 20epithelial cervical cancer patients with positive HPV-16 infection as the case group and 20 non-cervical cancer patients with positive HPV-16 infection as the control group. Women infected by HPV-16 with LMP-7 gene polymorphism had a higher risk (OR=7.36, CI 95%=1.38-40.55, p=0.013) to be diagnosed with cervical cancer. Balinese women who were infected by HPV-16 with TAP-2 gene polymorphism had a higher risk (OR= 9.33, CI 95%=2.18-39.96, p=0.001) to be diagnosed with cervical cancer. Meanwhile, Balinese women who were infected by HPV-16 with LMP-7 and TAP-2 genes polymorphism had a higher risk (OR=12.67, CI 95%=1.40-114.42, p=0.020) to be diagnosed with cervical cancer. As the result, it was shown that both of this gene polymorphism was working synergistically. Conclusion: TAP-2 and LMP-7 genes polymorphism play a role in the carcinogenesis mechanism of cervical cancer that is caused by HPV-16 infection in Bali. Meanwhile, LMP-2 and TAP-1 genes polymorphism were not found to play a role in the immunology pathway of cervical cancer that is caused by HPV-16 infection.

Association of TAP1 and TAP2 genes with susceptibility to pulmonary tuberculosis in Koreans.

Tuberculosis remains an important public health problem in Koreans. However, very few studies have reported on the genetic factors associated with TB susceptibility in Koreans. The aim of this study was to elucidate the genetic factors associated with susceptibility to pulmonary tuberculosis (PTB). We investigated the transporter associated with antigen processing -1 (TAP1) and TAP2 gene polymorphisms in 160 Korean PTB patients (categorized according to extent of lesion and TB medication history) and 210 controls. TAP2*C/E frequency was significantly increased in the PTB (pc = 0.004, OR = 2.28). TAP2*Bky2/C/E were enriched in the retreated, far-advanced and total PTB compared with the controls (pc = 0.015, OR = 3.27; pc = 0.019, OR = 2.56; pc = 2.8 × 10(-4) , OR = 2.42, respectively). In the comparison of TAP2 gene with the DRB1*08:03, which is associated with TAP2*Bky2 and PTB in Koreans, we demonstrated the hierarchy of these association factors. TAP2*C/E is independent factors as strong as DRB1*08:03, and TAP2*C/E interacts with DRB1*08:03, resulting in a striking combined association. Our results suggest that TAP2 gene has an association with PTB susceptibility, the extent of the lesion or recurrence. These associations are independent from and additive with DRB1*08:03.

Association between TAP1 gene polymorphisms and alopecia areata in a Korean population.

The transporter 1 ATP-binding cassette sub-family B (MDR/TAP) gene (TAP1) is located in the major histocompatibility complex class II region, and forms a heterodimer that plays a key role in endogenous antigen presentation pathways. Investigation of polymorphisms identified in these loci has revealed an association with several autoimmune disorders. Alopecia areata (AA) is a common autoimmune disease resulting from T cell-induced damage to hair follicles. The present study documents for the first time a comparison between the allelic and genotypic frequencies of TAP1 single nucleotide polymorphisms (SNPs) in patients with AA and those of a control group, using a direct sequencing method. Our results suggest an association between a promoter SNP (rs2071480) and susceptibility to this disease.

Association of TAP1 and TAP2 Gene Polymorphisms with Hematological Malignancies

Transporter associated with antigen presenting (TAP) 1 and TAP2 genes are localized in the major histocompatability complex (MHC) class II region and form a heterodimer playing a key role in endogenous pathways for antigen presentation. Defects of these genes have been reported to be common in different types of cancer. Polymorphisms identified in these loci have also been investigated and reported to be associated with several autoimmune disorders, viral infections and neoplasms. In the present study, for the first time, the allele and genotype frequencies of TAP1-333, TAP2-565, TAP2-651 and TAP2-665 were determined in patients with hematological malignancies (HM) using a PCR-RFLP method and compared with the frequencies in the control group. Our results suggested an association of TAP1-333 polymorphism with multiple myeloma-MM and TAP2- 565 polymorphism with chronic lymphoid leukemia-CLL. In addition, it could be concluded that the TAP2-665 GG genotype might be a risk factor for all types of hematological malignancies included in this study.

Association between polymorphisms of PSMB8, PSMB9 and TAP2 genes with rheumatoid arthritis in ethnic Han Chinese from Yunnan

To assess the association between single nucleotide polymorphisms (SNPs) of PSMB8, PSMB9 and TAP2 genes and rheumatoid arthritis (RA) in ethnic Han Chinese from Yunnan.A case-control study was carried out using 177 RA patients and 288 healthy controls. Genotypes of rs2071543, rs55745125 and rs138635403 loci of PSMB8 gene, and rs17587 locus of PSMB9 gene were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). And a polymerase chain reaction amplification refractory mutation system (ARMS-PCR) was used for typing rs2228396 locus of TAP2 gene. Genotypic and allelic frequencies were calculated. An Epi Info 7 software was used to calculate the Odds Ratio (OR) of above SNPs between the two groups.Allelic and genotypic frequencies of rs138635403 and rs17587 loci have differed significantly between the two groups (P<0.05). The frequency of GG genotype for rs17587 locus was also higher in the RA group (0.672) compared with control group (0.524) (OR=1.862, 95%CI: 1.261-2.749).Genetic polymorphisms of rs17587 appeared to be associated with RA in ethnic Han Chinese from Yunnan.

Genetic polymorphisms in MHC-encoded antigen processing gene TAP2: A case–control study in end-stage renal disease patients of North India

Aim TAP2 genes are involved in antigen presentation by MHC class I molecules, especially in the transport of endogenous peptides. As for most MHC genes, a polymorphism has been described and the possibility that it could influence the recipient immune response by modulating antigen presentation in renal disorders. The aim of our study was to analyze TAP2 gene polymorphism in between ESRD (end stage renal disease) patients and healthy controls in our North Indian population. Materials and method We analyzed 3 polymorphisms in the TAP2 gene viz. 565 (G → A, Ala → Thr), 379 (G → A, Val → Ile) and 665 (A → G, Thr → Ala), by amplification refractory mutation system-polymerase chain reaction, (ARMS-PCR) methodology using SPSS 11.0 (Chicago, IL, U.S.A.) in a hospital based case–control study in 148 ESRD cases and 230 healthy controls. They were age and sex matched and were of similar ethnicity. Results Our results showed that only TAP2 G > A 379 Val/Ile was found to be significant for end stage renal disease patients. Furthermore, 2 haplotypes, Ile 379-Thr 665 and Ile 379-Ala 665 (p = 0.001; OR = 0.28 and p = 0.030; OR = 4.30 respectively) were also associated with the disease and on the other hand gene combination effect revealed protective pattern with ESRD (Val/Ile 379-Thr/Thr 665 p = 0.007; OR = 0.30). These results suggested that the currently described polymorphism in the limited coding region of TAP2 genes individually does not influence end stage renal disease risk. It however, proposes a strong link when in combination with each other. Conclusion The study suggests that the possibility exists that some alleles, in the TAP genes, might confer susceptibility or protection in patients with ESRD which might prove to be helpful in identifying individuals at a higher risk for progressive renal insufficiency.

TAP1 and TAP2 gene polymorphisms in childhood cystic echinococcosis

The incidence of cystic echinococcosis (CE) due to Echinococcus granulosus is as high as 2000–2500 patients per year in Turkey. Whether genetic characteristics of the Turkish population cause a tendency to the disease is currently unknown. We aimed at studying the role of TAP gene polymorphisms in Turkish children with cystic echinococcosis. For an overview of allelic distribution of TAP1 and TAP2 genes, genotypes of 85 patients with CE and 100 controls were studied. To determine the genotype–phenotype correlation, 81 of the patients whose clinical data were available were analyzed. For TAP1-637, Asp/Gly heterozygosity was significantly more prevalent in CE patients than in controls (20 vs. 4%, odds ratio 6.0), while Gly/Gly homozygosity was less frequent (5 vs. 14%). For TAP2-379, Ile/Val heterozygosity was significantly more prevalent in CE patients than in controls (14 vs. 1%, odds ratio 16.27), while Ile/Ile homozygosity was less frequent (13 vs. 25%). TAP1-637 and TAP2-379 polymorphisms may have a role in causing genetic tendency for CE in children. The data may reflect the genetic properties of the Turkish population or may reveal the minor role of TAP gene polymorphisms in CE.

Correlation of Tap2 gene polymorphisms and genetic factors with esophageal cancer in Kazakh population in Xinjiang Uygur Autonomous Region

Correlation of Tap2 gene polymorphisms and genetic factors with esophageal cancer in Kazakh population in Xinjiang Uygur Autonomous Region

Polymorphisms of the TAP2 Genes in Chinese Patients with Systemic Lupus Erythematosus in Taiwan

Objective: The purpose of this study was to determine how polymorphisms of transporter associated with antigen processing 2 (TAP2) alleles contribute to the pathogenesis of systemic lupus erythematosus (SLE) in Taiwan. Methods: We enrolled 84 patients with SLE and 105 healthy controls. The polymorphisms were detected by polymerase chain reaction (PCR)-based restriction analysis. The relationships between SLE and TAP2 polymorphisms were evaluated. Results: No significant differences were found between normal subjects and SLE in TAP2-1 (p=0.28), TAP2-2 (p=0.55) and TAP2-3 (p=0.52) polymorphisms. However, the G allele of TAP2-1 was significantly more common than the A allele in cutaneous manifestations of SLE patients (malar rash, χ^2=6.90, p=0.001; discoid rash, χ^2=5.10, p=0.02; and photosensitivity, χ^2=5.80, p=0.02). Similarly, The G allele of TAP2-1 had a statistic significance than A allele in positive ANA of SLE patients (χ^2=9.35, p=0.002). Conclusion: Our data indicate that TAP2-1, TAP2-2 and TAP2-3 polymorphisms are not candidate genetic markers of SLE. However, the G allele of TAP2-1 may serve as a marker for cutaneous manifestations (malar rash, discoid rash and photosensitivity) and positive ANA in SLE patients.

Polymorphisms of the TAP 1 and 2 Gene May Influence Clinical Outcome of Primary Dengue Viral Infection

Antigen peptides are actively transported across the endoplasmic reticulum by the transporters associated with antigen presentation (TAP). TAP genes polymorphism could influence the selection process that determines which antigen peptides play a role in the pathogenesis of dengue infection. The aim of this study was to investigate the association of TAP genes polymorphism in diverse pathogenesis of dengue infection. This study included 197 dengue-infected patients who were further categorized into 64, 23 and 11 primary dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) cases, respectively and 26, 52, and 21 secondary DF, DHF and DSS cases, respectively as per WHO grading system. TAP1 and 2 gene polymorphisms were performed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Analysis of TAP1 gene polymorphism demonstrated decreased frequency of Ile/Ile genotype at TAP1(333) in primary DHF cases (39.1%) when compared with primary DF (64.1%, P < 0.034, OR = 0.611). The genotype frequency of Val/Val at TAP2(379) locus was significantly decreased among primary DHF (43.5%) in comparison to primary DF (71.9%, P = 0.015, OR = 0.605). Significant low proportion of primary DSS were found to have TAP1(637) Asp/Asp genotypes (54.5%) when compared with primary DF (70.3%, P = 0.043). Asp/Asp genotype at TAP1(637) was found to reduce the risk by 0.643 times for primary DSS. There was no significant difference in the genotypes studied between primary and secondary infection and also within secondary dengue infection in all three clinical groups. This report on TAP gene polymorphisms in dengue suggested that among the primary-infected individuals, homozygous patterns for Ile at TAP1(333) Val at TAP2(379) loci and Asp at TAP1(637) were found to be a protective factor against development of DHF and DSS, respectively.

Transporter associated with antigen processing (TAP) 1 gene polymorphisms in patients with hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a lung inflammatory disease caused by the inhalation of a variety of antigens. Previous studies support the role of the major histocompatibility complex (MHC) class II genes in the susceptibility to develop HP. However, the putative role of other MHC loci has not been elucidated. Transporters associated with antigen processing (TAP) genes are located within the MHC class II region and play an important role transporting peptides across the endoplasmic reticulum membrane for MHC class I molecules assembly. The distribution of single nucleotide polymorphisms (SNPs) in TAP1 genes was analyzed in 73 hypersensitivity pneumonitis (HP) patients and 58 normal subjects. We found a significant association of the allele Gly-637 (GGC) ( p = 0.00004, OR = 27.30, CI = 3.87–548.04) and the genotypes Asp-637/Gly-637 ( p = 0.01, OR = 16.0, CI = 2.19–631.21), Pro-661/Pro-661 ( p = 0.006, OR = 11.30, CI = 2.28–75.77) with HP. A significant decrease in the frequency of the allele Pro-661 (CCA) ( p = 0.008, OR = 0.06, CI = 0–0.45), the genotype Asp-637/Asp-637 ( p = 0.01, OR = 0.17, 95% CI = 0.05–0.58) and the haplotype [Val-333 (GTC), Val-458 (GTG), Gly-637 (GGC), Pro-661 (CCA)] was detected in HP patients compared with controls ( p = 0.002, OR = 0.07, CI = 0.0–0.57). These findings suggest that TAP1 gene polymorphisms are related to HP risk, and highlight the importance of the MHC in the development of this disease.

Significance of Transporter Associated with Antigen Processing 2 (TAP2) Gene Polymorphisms in Susceptibility to Dengue Viral Infection

The polymorphic transporter associated with antigen processing (TAP)1 and TAP2 genes encode subunits of the transporter that delivers peptides to the human leukocyte antigen class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We recently reported that TAP1 gene polymorphism is associated with severe dengue infection. This study was carried out to elucidate whether TAP2 polymorphisms are involved in diverse pathogenesis of dengue infection. This study included 100 controls and 197 dengue-infected patients who were further categorized into 90 dengue fever (DF) cases, 75 dengue hemorrhagic fever cases (DHF), and 32 dengue shock syndrome (DSS) cases as per WHO grading system. TAP2 gene polymorphisms were determined by amplification refraction mutation system-polymerase chain reaction. The frequency of isoleucine at TAP2 379 (34.5%) was increased among DHF in comparison to controls (21%, P = 0.014). DHF cases were more likely to be heterozygous at TAP2 379 (50.7%) than controls [24%, odds ratio (OR) = 2.11, P = 0.001]. Significantly high proportion of DHF was found to have TAP2 665 threonine/alanine (THR/ALA) genotypes (30.7%) when compared with DF (13.3%, OR = 2.3, P = 0.006) cases. There was no difference in the genotypes studied between DSS and controls or DF or DHF. This first report on TAP 2 gene polymorphism in dengue suggested that heterozygous pattern at TAP2 379 locus confers susceptibility to DHF, and TAP2 665 THR/ALA genotype was found to be a risk factor for development of DHF.