Characterization of the loricrin (<i>LOR</i>) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus

Giardina, Emiliano; Capon, Francesca; Rosa, Maria Cristina De; Mango, Ruggiero; Zambruno, Giovanna; Orecchia, Angela; Chimenti, Sergio; Giardina, Bruno; Novelli, Giuseppe

doi:10.1046/j.1529-8817.2004.00118.x

Cited by 35 publications

(30 citation statements)

References 27 publications

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“…We failed to identify sequence disease-specific variants. However, we confirmed the existence of SNPs previously characterized [9] . We typed SNPs (rs943967; rs6661601; rs12136773) using allele/haplotype TDT analysis.…”

Section: Resultssupporting

confidence: 89%

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Co-Localization of Susceptibility Loci for Psoriasis (PSORS4) and Atopic Dermatitis (ATOD2) on Human Chromosome 1q21

Giardina¹,

Sinibaldi²,

Chini³

et al. 2006

Hum Hered

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Psoriasis (PS) is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently associated with respiratory atopy. These diseases are associated with distinct immunologic abnormalities and represent typical examples of complex diseases triggered by both genetic and environmental factors, as demonstrated by independent twin studies. Genome wide linkage studies have mapped susceptibility loci on several chromosomes (PSORS1–9; ATOD1–5). Four of them overlap on chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and these two diseases rarely occur together in the same patient. An association fine-mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and 120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co-localization within an interval of 42 kb. This genomic interval contains a single gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and coding regions did not show evidence of association in neither of the two diseases. However, expression profiles of LOR in skin biopsies have shown reduced levels in PS and increased levels in ATOD, suggesting the existence of a specific misregulation in LOR mRNA production.

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Section: Resultssupporting

confidence: 89%

“…Locus overlapping was recently excluded for ATOD4 and PSORS2 on chromosome 17q25 [8] . Here, we report the results of linkage disequilibrium analyses which support a co-localization of PSORS4 and ATOD2 loci on human chromosome 1q21 and provided for the first time the evidence of an involvement of the LOR [9] gene in the pathogenesis of both disorders.…”

supporting

confidence: 53%

Co-Localization of Susceptibility Loci for Psoriasis (PSORS4) and Atopic Dermatitis (ATOD2) on Human Chromosome 1q21

Giardina¹,

Sinibaldi²,

Chini³

et al. 2006

Hum Hered

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“…These two disorders are polygenic and reactive to psychosocial stressors. Susceptibility to psoriasis has been associated to the area of chromosome 1q21 (PSORS4) that encodes PSMB4, 30 and susceptibility to asthma and nasal polyps (O(MIM) MIM 208550) 14 has been associated with functional promoter SNPs in TBX21 (À1993T/C), in chromosome 17q21.3.…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping of SNPs was performed using a SEQUENOM MassARRAY MALDI-TOF mass spectrometer (Sequenom, San Diego, CA, USA) for analysis of unlabeled single-base extension minisequencing reactions 27 or using the Golden Gate assay (Illumina, San Diego, CA, USA) as part of a multiplex reaction as previously described. 26 Our SEQUENOM protocol implemented the very short extension method proposed by Sun and colleagues 30 whereby sequencing products are extended by only one base for three of the four nucleotides (due to the presence of dideoxynucleotides for three of the four nucleotides in the minisequencing reaction) and by several additional bases for the fourth nucleotide (specified in advance so as to represent one of the two alleles at a given SNP locus). This allowed for clearly delineated mass separation of the two allelic variants at a given locus.…”

Section: Methodsmentioning

confidence: 99%

Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

et al. 2008

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There are clinical parallels between the nature and course of depressive symptoms in major depressive disorder (MDD) and those of inflammatory disorders. However, the characterization of a possible immune system dysregulation in MDD has been challenging. Emerging data support the role of T-cell dysfunction. Here we report the association of MDD and antidepressant response to genes important in the modulation of the hypothalamic-pituitaryadrenal axis and immune functions in Mexican Americans with major depression. Specifically, single nucleotide polymorphisms (SNPs) in two genes critical for T-cell function are associated with susceptibility to MDD: PSMB4 (proteasome b4 subunit), important for antigen processing, and TBX21 (T bet), critical for differentiation. Our analyses revealed a significant combined allele dose-effect: individuals who had one, two and three risk alleles were 2.3, 3.2 and 9.8 times more likely to have the diagnosis of MDD, respectively. We found associations of several SNPs and antidepressant response; those genes support the role of T cell (CD3E, PRKCH, PSMD9 and STAT3) and hypothalamic-pituitary-adrenal axis (UCN3) functions in treatment response. We also describe in MDD increased levels of CXCL10/IP-10, which decreased in response to antidepressants. This further suggests predominance of type 1 T-cell activity in MDD. T-cell function variations that we describe here may account for 47.8% of the attributable risk in Mexican Americans with moderate MDD. Immune function genes are highly variable; therefore, different genes might be implicated in distinct population groups.

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“…The EDC includes members of S100 and small proline-rich region (SPRR) gene clusters and cornified envelope genes known to be structurally related to SPRR or S100 genes, including filaggrin, trichohyalin, loricrin and involucrin. Among these genes, loricrin[26], S100A2 [27] and S100A7 [28] are excluded as candidates for the PSORS4 locus. A recent study revealed that the association of psoriasis to the PGLYRP and SPRR genes at the PSORS4 locus on 1q21 shows heterogeneity among Finnish, Swedish and Irish families [29].…”

Section: Discussionmentioning

confidence: 99%

The Association between the IL-20 –1723C→G Allele on the 1q Chromosome and Psoriasis Triggered or Exacerbated by an Upper Respiratory Tract Infection in the Chinese Han Population

Chen

Jin²,

Chen³

et al. 2010

Dermatology

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Background: Psoriasis is a cutaneous disorder of multifactorial etiology influenced by both genetic and environmental factors such as infection. Methods: We conducted a genome analysis with 20 microsatellite markers spanning the long arm of chromosome 1 in 36 Chinese families with psoriasis and detected evidence for linkage at 1q21 with a nonparametric linkage score of 1.74, p = 0.03, and 1q32 with one of 1.84, p = 0.03. According to the positional and functional candidate principle, we further investigated the single-nucleotide polymorphisms of the HAX-1 gene (located in 1q21) and IL-20 gene (located in 1q32) in a case-control study including 340 sporadic patients and 199 controls. Results: We determined that the frequency of the G allele of IL-20 –1723C→G (rs1713239) was significantly higher among psoriatic patients (38.5% in cases vs. 31.2% in controls, p = 0.015, odds ratio, OR = 1.39, 95% confidence interval, CI = 1.07–1.80). When we stratified our analysis by psoriasis triggered or exacerbated by infection of the upper respiratory tract, a significant difference was detected (42.4% in stratified cases vs. 31.2% in controls, p = 0.005, OR = 1.63, 95% CI = 1.15–2.30). Conclusion: We assume that triggered or exacerbated by respiratory tract infection, the population with the G allele of IL-20 –1723C→G are predisposed to psoriasis.

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Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus

Cited by 35 publications

References 27 publications

Co-Localization of Susceptibility Loci for Psoriasis (PSORS4) and Atopic Dermatitis (ATOD2) on Human Chromosome 1q21

Co-Localization of Susceptibility Loci for Psoriasis (PSORS4) and Atopic Dermatitis (ATOD2) on Human Chromosome 1q21

Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

The Association between the IL-20 –1723C→G Allele on the 1q Chromosome and Psoriasis Triggered or Exacerbated by an Upper Respiratory Tract Infection in the Chinese Han Population

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