Abstract
To explore the effect of A/G polymorphisms at codon 637 of the transporter associated with antigen processing 1 (TAP1) gene on the risk of hypertension. A case-control study of epidemiology was conducted. The case group included 277 community-based patients (136 males and 141 females; mean age 58.7±12.1 years) diagnosed with hypertension, and the control group consisted of 227 healthy subjects (95 males and 132 females; mean age 51.29±12.16 years) from the same community. The A/G polymorphisms at codon 637 of the TAP1 gene was examined by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA. The effect of A/G polymorphisms at codon 637 of the TAP1 gene on hypertension was analyzed by using multivariate unconditional logistic regression models. The contribution of TAP1 637 A/G allele frequencies of the control group was consistent with that predicted by the Hardy-Weinberg equilibrium test (x2=230, p=0.632). There was a significant difference in the frequency of the A/G polymorphisms at codon 637 of the TAP1 gene between hypertensive patients (74.4/25.6%) and controls (82.4%/17.6%), x2=9.324, p=0.002. Genotype model (AA-AG-GG) analysis showed that there was a significant difference in the frequency of the recessive genotype between cases and controls (AA/AG vs. GG: odds ratio [OR]=3.046, 95% confidence interval [CI]=1.138–8.153) after adjustment for the covariates of age, serum total cholesterol, triglycerides, body mass index (BMI) and smoking. But there were no significant differences in the frequency of the genotype for the dominant model (AA vs. AG/GG: p=0.293) or additive model (AA vs. AG vs. GG: p=0.081) after adjustment. One-way ANOVA analysis showed that the systolic blood pressure, diastolic blood pressure, and BMI levels of the GG genotype were significantly higher than those of the AA or AG genotypes. In conclusion, our findings suggest that the A/G polymorphisms at codon 637 of the TAP1 gene contributes to the risk of hypertension, possibly via the increases in blood pressure and BMI.
Similar content being viewed by others
Article PDF
References
Lifton RP, Gharavi AG, Geller DS : Molecular mechanisms of human hypertension. Cell 2001; 104: 545–556.
Liu W, Zhao W, Chase GA : Genome scan meta-analysis for hypertension. Am J Hypertens 2004; 17: 1100–1106.
Benjafield AV, Wang WY, Speirs HJ, et al: Genome-wide scan for hypertension in Sydney Sibships: the GENIHUSS study. Am J Hypertens 2005; 18: 828–832.
Kokubo Y, Tomoike H, Tanaka C, et al: Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension. Hypertens Res 2006; 29: 611–619.
Nakanishi K : Analysis of TAP gene in IDDM. Nippon Rinsho 1994; 52: 2762–2766.
Zukowska-Szczechowska E, Tomaszewski M, Grzeszczak W : Role of advanced glycosylation end products in the pathogenesis of hypertension. Przegl Lek 2003; 60: 585–587.
Wang X, Desai K, Clausen JT, et al: Increased methylglyoxal and advanced glycation end products in kidney from spontaneously hypertensive rats. Kidney Int 2004; 66: 2315–2321.
Oshima T, Ozono R, Yano Y, et al: Beneficial effect of T-type calcium channel blockers on endothelial function in patients with essential hypertension. Hypertens Res 2005; 28: 889–894.
Mori Y, Ohyanagi M, Koida S, et al: Effects of endothelium-derived hyperpolarizing factor and nitric oxide on endothelial function in femoral resistance arteries of spontaneously hypertensive rats. Hypertens Res 2006; 29: 187–195.
Yang Z, Venardos K, Jones E, et al: Identification of a novel polymorphism in the 3′UTR of the L-arginine transporter gene SLC7A1. Contribution to hypertension and endothelial dysfunction. Circulation 2007; 115: 1269–1274.
Alberts P, Daumke O, Deverson EV, et al: Distinct functional properties of the TAP subunits coordinate the nucleotide-dependent transport cycle. Curr Biol 2001; 11: 242–251.
Ritz U, Drexler I, Sutter D, et al: Impaired transporter associated with antigen processing (TAP) function attributable to a single amino acid alteration in the peptide TAP subunit TAP1. J Immunol 2003; 170: 941–946.
Gao MY, Wu AH, Wen CX, et al: Investigating the correlation between polymorphisms with couple sharing rate of TAP gene and hypertensive disorder complicating pregnancy. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2006; 23: 165–168.
Daumke O, Knittler MR : Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is determined by intrinsic properties of the nucleotide binding domains. Eur J Biochem 2001; 268: 4776–4786.
Saeki H, Kuwata S, Nakagawa H, et al: Analysis of disease-associated amino acid epitopes on HLA class II molecules in atopic dermatitis. J Allergy Clin Immunol 1995; 96: 1061–1068.
Trowsdale J, Ragoussis J, Campbell RD : Map of the human MHC. Immunol Today 1991; 12: 443–446.
Lankat-Buttgereit B, Tampe R : The transporter associated with antigen processing: function and implications in human diseases. Physiol Rev 2002; 82: 187–204.
Furukawa H, Murata S, Yabe T, et al: Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome. J Clin Invest 1999; 103: 755–758.
Colonna M, Bresnahan M, Bahram S, et al: Allelic variants of the human putative peptide transporter involved in antigen processing. Proc Natl Acad Sci U S A 1992; 89: 3932–3936.
Russ G, Esquivel F, Yewdell JW, et al: Assembly, intracellular localization, and nucleotide binding properties of the human peptide transporters TAP1 and TAP2 expressed by recombinant vaccinia viruses. J Biol Chem 1995; 270: 21312–21318.
Marsh SG : Nomenclature for factors of the HLA system, update June 2005. Hum Immunol 2005; 66: 1025–1027.
Powis SH, Tonks S, Mockridge I, et al: Alleles and haplotypes of the MHC-encoded ABC transporters TAP1 and TAP2. Immunogenetics 1993; 37: 373–380.
Takeuchi F, Kuwata S, Nakano K, et al: Association of TAP1 and TAP2 with systemic sclerosis in Japanese. Clin Exp Rheumatol 1996; 14: 513–521.
Maruya E, Ishikawa Y, Lin L, et al: New polymorphisms within human TAP2 in the ATP-binding domain and profiles of TAP polymorphism in Japanese. MHC 1996; 3: 1–8.
Whang DH, Park H, Roh EY, et al: TAP1 and TAP2 gene polymorphisms and HLA-TAP haplotypes in Koreans based on 90 families. Hum Immunol 2005; 66: 998–1007.
Pyo CW, Hur SS, Kim YK, et al: Association of TAP and HLA-DM genes with psoriasis in Koreans. J Invest Dermatol 2003; 120: 616–622.
Hohler T, Weinmann A, Schneider PM, et al: TAP-polymorphisms in juvenile onset psoriasis and psoriatic arthritis. Hum Immunol 1996; 51: 49–54.
Teisserenc H BL, Briaud I, Busson M, Albert E, Bignon JD : TAP, LMP and HLA-DM polymorphism: 12th International Histocompatibility Workshop Study, in Charron D ( ed): Genetic Diversity of HLA—Functional and Medical Implications. Paris, EDK, Medical and Scientific International Publisher, 1997, p 159.
Cucca F, Congia M, Trowsdale J, et al: Insulin-dependent diabetes mellitus and the major histocompatibility complex peptide transporters TAP1 and TAP2: no association in a population with a high disease incidence. Tissue Antigens 1994; 44: 234–240.
Witkowska-Tobola AM, Szczerkowska-Dobosz A, Nedoszytko B, et al: Polymorphism of the TAP1 gene in Polish patients with psoriasis vulgaris. J Appl Genet 2004; 45: 391–393.
Ismail A, Bousaffara R, Kaziz J, et al: Polymorphism in transporter antigen peptides gene (TAP1) associated with atopy in Tunisians. J Allergy Clin Immunol 1997; 99: 216–223.
Ozbas-Gerceker F, Ozguc M : Frequencies of TAP1 and TAP2 gene polymorphisms in the Anatolian population. Eur J Immunogenet 2003; 30: 97–99.
Barron KS, Reveille JD, Carrington M, et al: Susceptibility to Reiter's syndrome is associated with alleles of TAP genes. Arthritis Rheum 1995; 38: 684–689.
Chevrier D, Giral M, Braud V, et al: Effects of MHC-encoded TAP1 and TAP2 gene polymorphism and matching on kidney graft rejection. Transplantation 1995; 60: 292–296.
Zhang SL, Chabod J, Penfornis A, et al: TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in eastern France. Eur J Immunogenet 2002; 29: 241–249.
Moins-Teisserenc H, Semana G, Alizadeh M, et al: TAP2 gene polymorphism contributes to genetic susceptibility to multiple sclerosis. Hum Immunol 1995; 42: 195–202.
Djilali-Saiah I, Benini V, Daniel S, et al: Linkage disequilibrium between HLA class II (DR, DQ, DP) and antigen processing (LMP, TAP, DM) genes of the major histocompatibility complex. Tissue Antigens 1996; 48: 87–92.
Faucz FR, Probst CM, Petzl-Erler ML : Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversity. Eur J Immunogenet 2000; 27: 5–16.
Kuwata S, Yanagisawa M, Saeki H, et al: Lack of primary association between transporter associated with antigen processing genes and atopic dermatitis. J Allergy Clin Immunol 1995; 96: 1051–1060.
Ishihara M, Ohno S, Mizuki N, et al: Genetic polymorphisms of the major histocompatibility complex-encoded antigen-processing genes TAP and LMP in sarcoidosis. Hum Immunol 1996; 45: 105–110.
Lee HJ, Ha SJ, Han H, et al: Distribution of HLA-A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis. Clin Exp Allergy 2001; 31: 1867–1874.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shen, C., Guo, Z., Wu, M. et al. Association Study between Hypertension and A/G Polymorphism at Codon 637 of the Transporter Associated with Antigen Processing 1 Gene. Hypertens Res 30, 683–690 (2007). https://doi.org/10.1291/hypres.30.683
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1291/hypres.30.683
