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Chemical Compound Review:

Trp-Trp (2R)-2-[[(2R)-2-amino-3-(1H- indol-3...

Synonyms: SureCN11855463, CTK1E9330, AC1O52WJ, 58607-72-0, D-Tryptophan, N-D-tryptophyl-

Stern, M.C. et al., Okumura, K. et al., Allison, D.B. et al., Oizumi, T. et al., Smith, T.R. et al., et al.

Chen, Tang, Xue, Xu, Ma, Hsu, Cho, Stern, Siegmund, Corral, Haile, Kurokawa, Nakai, Kameo, Liu, Satoh, Malczewska-Malec, Wybrańska, Leszczyńska-Gołabek, Niedbał, Kwaśniak, Hartwich, Kieć-Wilk, Motyka, Szopa, Dembińska-Kieć, Tanahashi, Tabira,

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Disease relevance of Trp-Trp

Traits related to obesity, such as percent body fat (28.82 +/- 7.95 vs. 25.93 +/- 7.21, P = 0.038) and BMI (25.07 +/- 3.84 vs. 23.63 +/- 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups [1].
The risk of lung cancer increased more than additive interaction (adjusted OR = 8.77; CI 1.47-52.31) for the individuals with both putative high-risk genotypes of XRCC1 194 Trp/Trp and XPD 751 Lys allele [2].
High omega-6/omega-3 polyunsaturated fatty acid ratios were associated with adenoma risk among subjects with the XRCC1 codon 194 Arg/Arg and codon 399 Gln/Gln or the codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.026) [3].
Carriers of at least one variant allele of XRCC1 Arg194Trp [Arg/Trp and Trp/Trp versus Arg/Arg, odds ratio (OR) = 1.60, 95% confidence interval (CI) = 0.89-2.87] or two variant alleles of XRCC3 241Met/Metmay have an increased risk of breast cancer (Met/Met versus Thr/Thr and Thr/Met, OR = 1.54, 95% CI = 0.94-2.52) [4].

High impact information on Trp-Trp

Two distinct chromogranin B-derived peptides result from cleavage at Trp-Trp bonds, a site not typically associated with neuropeptide processing [5].
1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides [6].
The spectroscopic response upon refolding monitored by Trp fluorescence and the absence of a Trp/Trp exciton coupling apparent in the far-UV CD spectrum of the wild-type protein, however, indicated that the tertiary structure of the folded state for G95A DHFR is altered [7].
No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp [1].
There was a trend that the Arg/Arg had higher systolic blood pressure than the Trp/Trp in both groups, but the differences were not statistically significant [8].

Biological context of Trp-Trp

Furthermore, when compared to Arg/Arg and Arg/Trp genotype combined, homozygote for Trp/Trp genotype significantly increased the risk of developing ESCC, with the adjusted OR being 2.07 (95% CI 1.34-3.20) [9].
The weighted mean BMI difference between Trp/Trp homozygotes and Trp/Arg heterozygotes was 0.19 (s.e. = 0.11; P = 0.07) [10].
The genotype frequencies were: Trp/Trp, 71.3%; Try/Arg, 22.1%; and Arg/Arg, 6.6%, with allele frequencies of 0.82 for Trp64 and 0.18 for Arg64 [11].
The subjects with the Arg/Arg genotype had significantly higher levels of fasting plasma insulin and triglycerides and an insulin resistance index of homeostasis model assessment (HOMA-R), and significantly smaller LDL particle size than did the subjects with the Trp/Trp genotype [11].

Associations of Trp-Trp with other chemical compounds

Fe65L2 contains an N-terminal WW (Trp-Trp) domain followed by two phosphotyrosine-interaction domains, and consists of 486 amino acids [12].
Women with the Trp/Trp genotype of alpha-adducin Gly460Trp might have increased risk for cardiovascular diseases due to lower concentrations of serum bilirubin [13].
Patients with the Trp/Trp polymorphism in the b3-AR gene were characterized by higher glucose and insulin concentration during OGTT and higher blood concentration of FFA and TG during OLTT [14].

Gene context of Trp-Trp

Four diabetic patients carried the homozygous mutation (Thr/Thr) in the NeuroD1 gene and 3 patients carried the homozygous mutation (Trp/Trp) in the Pax4 gene, while both homozygous mutations were not detected in the control subjects [15].
After extraction of relevant data, main and subgroup meta-analyses were performed to assess the differences in IR indices between Trp/Trp and Trp/Arg genotypes [16].
However, low antioxidant intake was associated with an inverse association only among subjects with the XRCC1 codon 194 Arg/Trp or Trp/Trp and codon 399 Arg/Arg or Arg/Gln combined genotypes (P for interaction = 0.022), which was independent of unsaturated fat intake [3].
RESULTS: There were no differences in Trp64Arg genotype distribution between type 1 diabetic patients with diabetic nephropathy and type 1 diabetic patients with normoalbuminuria: 295 (88%)/38 (11%)/3 (1%) vs 161 (84%)/30 (16%)/- had Trp/Trp, Trp/Arg or Arg/Arg genotype respectively [17].
MEASUREMENTS: For each genotype of the beta3 adrenergic receptor (Trp/Trp; Trp/Arg; Arg/Arg), we extracted the number of subjects, mean and standard deviation of BMI from 23 studies, including 36 different subgroups with a total of 7399 subjects [10].

Analytical, diagnostic and therapeutic context of Trp-Trp

There were no significant differences in body mass index and percent body fat between the Arg carriers (Trp/Arg or Arg/Arg) and the Arg noncarriers (Trp/Trp) for either sex [18].

References

Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample. Oizumi, T., Daimon, M., Saitoh, T., Kameda, W., Yamaguchi, H., Ohnuma, H., Igarashi, M., Eguchi, H., Manaka, H., Tominaga, M., Kato, T. Diabetes Care (2001) [Pubmed]
DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Chen, S., Tang, D., Xue, K., Xu, L., Ma, G., Hsu, Y., Cho, S.S. Carcinogenesis (2002) [Pubmed]
XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk. Stern, M.C., Siegmund, K.D., Corral, R., Haile, R.W. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
DNA-repair genetic polymorphisms and breast cancer risk. Smith, T.R., Levine, E.A., Perrier, N.D., Miller, M.S., Freimanis, R.I., Lohman, K., Case, L.D., Xu, J., Mohrenweiser, H.W., Hu, J.J. Cancer Epidemiol. Biomarkers Prev. (2003) [Pubmed]
Identification of peptides from brain and pituitary of Cpe(fat)/Cpe(fat) mice. Che, F.Y., Yan, L., Li, H., Mzhavia, N., Devi, L.A., Fricker, L.D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
1H NMR study on the binding of Pin1 Trp-Trp domain with phosphothreonine peptides. Wintjens, R., Wieruszeski, J.M., Drobecq, H., Rousselot-Pailley, P., Buée, L., Lippens, G., Landrieu, I. J. Biol. Chem. (2001) [Pubmed]
The coordination of the isomerization of a conserved non-prolyl cis peptide bond with the rate-limiting steps in the folding of dihydrofolate reductase. Svensson, A.K., O'Neill, J.C., Matthews, C.R. J. Mol. Biol. (2003) [Pubmed]
Clinical features associated with the homozygous Trp64Arg mutation of the beta3-adrenergic receptor: no evidence for its association with obesity in Japanese. Sun, L., Ishibashi, S., Osuga, J., Harada, K., Ohashi, K., Gotoda, T., Fukuo, Y., Yazaki, Y., Yamada, N. Arterioscler. Thromb. Vasc. Biol. (1998) [Pubmed]
Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. Xing, D., Qi, J., Miao, X., Lu, W., Tan, W., Lin, D. Int. J. Cancer (2002) [Pubmed]
Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with body mass index. Allison, D.B., Heo, M., Faith, M.S., Pietrobelli, A. Int. J. Obes. Relat. Metab. Disord. (1998) [Pubmed]
The polymorphism of the beta3-adrenergic receptor gene is associated with reduced low-density lipoprotein particle size. Okumura, K., Matsui, H., Ogawa, Y., Takahashi, R., Matsubara, K., Imai, H., Imamura, A., Mizuno, T., Tsuzuki, M., Kitamura, Y. Metab. Clin. Exp. (2003) [Pubmed]
Characterization of an amyloid precursor protein-binding protein Fe65L2 and its novel isoforms lacking phosphotyrosine-interaction domains. Tanahashi, H., Tabira, T. Biochem. J. (2002) [Pubmed]
Significant associations of the alpha-adducin gene Gly460Trp polymorphism with serum bilirubin concentrations in Chinese essential hypertension patients. Yu, Y.X., Venners, S.A., Niu, T.H., Chen, C.Z., Huang, A.Q., Zhang, Y., Feng, Y., Li, D., Xing, H.X., Wu, D., Peng, S.J., Xu, X.P. Yi Chuan Xue Bao (2004) [Pubmed]
An analysis of the link between polymorphisms of the beta2 and beta3 adrenergic receptor gene and metabolic parameters among Polish Caucasians with familial obesity. Malczewska-Malec, M., Wybrańska, I., Leszczyńska-Gołabek, I., Niedbał, S., Kwaśniak, M., Hartwich, J., Kieć-Wilk, B., Motyka, M., Szopa, M., Dembińska-Kieć, A. Med. Sci. Monit. (2003) [Pubmed]
Beta-cell dysfunction in late-onset diabetic subjects carrying homozygous mutation in transcription factors NeuroD1 and Pax4. Kanatsuka, A., Tokuyama, Y., Nozaki, O., Matsui, K., Egashira, T. Metab. Clin. Exp. (2002) [Pubmed]
Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with insulin resistance. Zhan, S., Ho, S.C. Obes. Res. (2005) [Pubmed]
The Trp64Arg amino acid polymorphism of the beta3-adrenergic receptor gene does not contribute to the genetic susceptibility of diabetic microvascular complications in Caucasian type 1 diabetic patients. Tarnow, L., Urhammer, S.A., Mottlau, B., Hansen, B.V., Pedersen, O., Parving, H.H. Nephrol. Dial. Transplant. (1999) [Pubmed]
Relationship between the beta3-adrenoceptor gene variant and body fat in Japanese children. Kurokawa, N., Nakai, K., Kameo, S., Liu, Z.M., Satoh, H. Tohoku J. Exp. Med. (2003) [Pubmed]

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