Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3

Kato, Hitoshi; Tsuchiya, Naoyuki; Tokunaga, Katsushi

doi:10.1038/sj.gene.6363682

Cited by 25 publications

(22 citation statements)

References 47 publications

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“…The allele frequencies of the SNPs (IL8rb and IL8ra) within the IL8RB and IL8RA loci were similar to those reported for the Japanese. 41 On the other hand, the distribution pattern of allele frequencies for SNPs within the SLC11A1 gene is more interesting.…”

Section: Resultsmentioning

confidence: 99%

“…The strong LD between IL8ra and IL8rb was also demonstrated in the Japanese. 41 On the other hand, IL8rb exhibited significant LD with SLC1, SLC2 and SLC3 (|D 0 |B0.5), but not the other markers. This finding has great significance as will be discussed below.…”

Section: Genetic Markers Amentioning

confidence: 87%

“…RA was found associated with SLC6a and SLC6b but not with SLC1-SLC3 in two studies, 20,21 while no association was found between IL8rb and RA in another study. 41 Conclusions This is the first systematic study to investigate the LD pattern within and around the SLC11A1 locus. Markers within SLC11A1 are in significant LD with each other except SLC4, SLC6a and SLC6b.…”

Section: Decay Of Ldmentioning

confidence: 93%

“…Other nomenclature b Alleles (major/minor) c Allele frequencies (minor alleles) Other nomenclature refers to the alternative names of the genetic markers used in previous studies: IL8rb and IL8ra reported by Kato et al, 41 markers within the SLC11A1 gene by Liu et al 42 and Bellamy et al 14 In addition, the rs numbers refer to the reference SNP ID numbers used by dbSNP database, NCBI. The major allele refers to the more frequent allele and the minor allele the less frequent allele.…”

Section: Genetic Markers Amentioning

confidence: 99%

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Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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The SLC11A1 (or NRAMP1) locus on human chromosome 2q35 encodes for the protein solute carrier family 11, member 1. It is expressed in macrophages and involved in the early stages of macrophage priming and activation. Different association studies have shown that the SLC11A1 gene affects susceptibility to infectious diseases and autoimmune inflammatory diseases. Although functional SLC11A1 polymorphisms may account for its role in affecting the susceptibility to these diseases, the positive association can also be because of flanking polymorphisms showing linkage disequilibrium (LD) with this locus. This is the first systematic study to investigate the LD pattern within and around the gene. LD was investigated by genotyping 17 genetic markers in a Chinese population (n ¼ 360). The results indicate that LD is maintained at least 110 kb both upstream and downstream of the locus. The complex LD pattern demands that association studies with SLC11A1 should be carried out with both 5 0 and 3 0 markers. The strong LD between IL8RB and the 5 0 SLC11A1 markers also dictates that IL8RB be tested for association with these diseases. Thus, positive association with SLC11A1 should be interpreted cautiously, and IL8RB should also be considered as a potential candidate susceptibility gene unless proven otherwise.

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Section: Resultsmentioning

confidence: 99%

Section: Genetic Markers Amentioning

confidence: 87%

Section: Decay Of Ldmentioning

confidence: 93%

Section: Genetic Markers Amentioning

confidence: 99%

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Extent and distribution of linkage disequilibrium around the SLC11A1 locus

2003

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“…33 The SSCP conditions are listed in Table 4. The primer sets used for genotyping of À1283G4A, À871C4T, À514T4C, À353G4C, c.313G4A and IVS1-45C4G were Prom 1, Prom 2, Prom 4, Prom 5, Exon1-2 and Exon 2, respectively.…”

Section: Patients and Healthy Individualsmentioning

confidence: 99%

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

et al. 2002

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Recent studies indicated a substantial role of BLyS (BAFF, TNFSF13B) in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in humans and in animal models. This study was conducted to screen for polymorphisms of human BLYS, and to examine whether they are involved in the genetic susceptibility to human SLE and RA. A systematic polymorphism screening was performed in the coding region, 5 0 and 3 0 untranslated regions, and promoter region of human BLYS. Association of the detected polymorphisms with SLE and RA was analyzed in 221 Japanese patients with RA, 156 with SLE, and 227 healthy individuals, using the case-control approach. Four single nucleotide polymorphisms (SNPs) in the promoter, one SNP in intron 1, and one rare nonsynonymous substitution (Ala105Thr) in the coding region were detected. The BLYS SNPs were found to form three common haplotypes. Significant association with the susceptibility to SLE or RA was not observed. However, a tendency for the increase of À871T/T genotype was observed in SLE patients with anti-Sm antibody (P ¼ 0.082). BLYS mRNA level was significantly elevated in the monocytes from individuals carrying À871T (P ¼ 0.010). In addition, although statistically not significant, 105Thr allele was slightly increased in patients with RA compared with controls (P ¼ 0.058). Characterizing the functional and clinical significance of these new SNPs requires further study.

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Computational studies of CXCR1, the receptor of IL‐8/CXCL8, using molecular dynamics and electrostatics

et al. 2007

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The three-dimensional structure of IL-8/CXCL8 has been previously determined using NMR spectroscopy and X-ray crystallography, but the structure of the receptors for this chemokine has not been determined experimentally. We present here the development of a model for the structure of the IL-8/CXCL8 receptor CXCR1, using a combination of homology modeling and a molecular dynamics simulation. Based on this model, we discuss the analysis of structural, dynamic, and physicochemical properties of CXCR1. We focused on the role of pairwise ionic interactions in local structural stability of CXCR1 and the role of electrostatic potentials in recognition of CXCR1 with IL-8/CXCL8. We have performed theoretical mutations of six charged amino acids in CXCR1, which abolish binding as suggested by earlier experimental data, to shed light on the effect of charge on association ability. We propose that the observed loss of binding in the six CXCR1 mutants is owed to loss of local structural stability, rather than hindrance of the recognition process because of changes in the overall electrostatic properties of the receptor. Based on further structural analysis, we propose some mutations of charged residues involving ion pairs in different elements of transmembrane helices and extracellular loops, which are expected to alter the local structure and possibly affect binding.

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Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3

Cited by 25 publications

References 47 publications

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

Computational studies of CXCR1, the receptor of IL‐8/CXCL8, using molecular dynamics and electrostatics

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