Eotaxin gene single nucleotide polymorphisms in the promoter and exon regions are not associated with susceptibility to atopic dermatitis,but two of them in the promoter region are associated with serum IgE levels in patients with atopic dermatitis

Eotaxin is believed to play an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and Th2 lymphocytes. The eotaxin gene is located at chromosome 17q21.1-q21.2, and linkage findings of AD on chromosome 17 were reported. Recently we have identified single nucleotide polymorphisms (SNPs) of eotaxin gene (-426C > T, -384A > G, 67G > A). To learn whether eotaxin gene SNPs are associated with susceptibility to AD or phenotypes of AD, we investigated the genotype frequencies at each SNP of the gene in AD patients and in controls. We examined 140 Japanese AD patients and 140 healthy Japanese individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. No significant difference was observed in allele or genotype frequencies of any SNP between AD patients and controls. Serum immunoglobulin E (IgE) levels were significantly lower in CT and TT genotype than in CC (P = 0.038) in -426C > T SNP, and lower in GG than in AA and AG with borderline significance (P = 0.053) in -384A > G SNP in AD patients. Eotaxin gene SNPs in the promoter and exon regions are not associated with susceptibility to AD, but two of them in the promoter region are associated with phenotype of AD.     

Investigation of the eotaxin gene -426C-->T, -384A-->G and 67G-->a single-nucleotide polymorphisms and atopic dermatitis in Italian children using family-based association methods.

BACKGROUND: Eotaxin plays an important role in atopic dermatitis (AD) as a potent chemoattractant and activator of eosinophils and T-helper 2 lymphocytes. AIM: To investigate whether single-nucleotide polymorphisms of the eotaxin gene are associated with AD, we investigated the genotype and allelic frequencies of -426C-->T, -384A-->G, and 67G-->A SNPs in 130 Italian families. METHODS: In total, 130 children with either the extrinsic allergic or intrinsic nonallergic forms of AD (EAD and IAD) were recruited from 130 families. Genotyping was performed using PCR and restriction fragment length polymorphism analysis. RESULTS: A significant difference was observed in the genotype frequency of the -426C-->T SNP between children with EAD and those with IAD (P = 0.01), and between children with EAD and controls (P = 0.01). The allele frequencies of the -426C-->T SNP were significantly different between children with EAD and those with IAD (P < 0.01), and between children with EAD and controls (P < 0.01). For children with EAD, the genotype frequency of the -426C-->T SNP was no different between the groups with mild, moderate and severe SCORAD (P = NS). No significant association was observed between the -384A-->G and 67G-->A SNPs and the two groups of children with EAD and IAD compared with the control group. In 32 trios selected from 68 EAD families, the transmission disequilibrium test showed a preferential transmission of the -426T allele from the parents to affected offspring (P < 0.01). CONCLUSIONS: Our results suggest that in our group of children with AD, the eotaxin gene may play a crucial role in the development of extrinsic AD, probably with other genetic factors.     

Association of thymic stromal lymphopoietin gene −847C>T polymorphism in generalized vitiligo

Abstracts: Thymic stromal lymphopoietin (TSLP) induces naïve CD4+ T cells to produce Th2 cytokines. In addition, to low production of Th2 cytokines, strong Th1 response, which plays an important role in vitiligo development, has been induced by blockade of TSLP or TSLP receptor. This study examined whether a functional TSLP polymorphism was associated with vitiligo. One hundred and sixty Korean patients with vitiligo and 568 healthy Korean individuals were examined for the four SNPs of TSLP gene. Luciferase activity was measured for promoter assay. The genotype and allele frequencies of ?847C>T polymorphism were lower in vitiligo patients compared with the controls, whereas those of wild type were higher (P = 0.004, P = 0.017 respectively). None the less, the promoter activity of ?847C decreased significantly (P = 0.013) compared with ?847T, expecting lower TSLP mRNA levels in the polymorphism. Collectively, C allele at the TSLP ?847C>T polymorphism may increase susceptibility to generalized vitiligo through decreasing TSLP mRNA expression levels.     

Interleukin-13 gene polymorphism G4257A is associated with atopic dermatitis in Japanese patients

Interleukin (IL)-13 plays an important role in the induction of immunoglobulin E (IgE) and in the pathogenesis of atopic dermatitis (AD). We investigated the allele and genotype frequencies of three IL-13 single nucleotide polymorphisms (SNPs) (A704C and C1103T in the promoter region and G4257A in exon 4) in Japanese patients with AD. For A704C and C1103T SNPs, there were no significant differences in allele or genotype frequencies between AD patients and controls. For G4257A SNP, A allele was significantly increased in AD patients (39.5%) compared with controls (29.4%) (P = 0.016). The same proportion of each genotype and allele was observed in the patient subgroup with and without asthma. Serum IgE levels and peripheral eosinophil counts were not significantly different among genotypes in G4257A SNP. There was also no significant difference in allele or genotype frequencies between AD patients with mild disease and those with severe disease, between those with family history of AD and those without it, or between those with family history of atopic disorders and those without it. This result suggests that 4257A allele is associated with susceptibility to AD and that it may function in the pathogenesis of AD itself, presumably by other mechanisms than inducing IgE production.     

Interleukin-12 p40 gene (IL12B) 3'-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris

Interleukin-12 (IL-12) is believed to play an important role in inducing Th1-type cytokine profiles. Atopic dermatitis (AD) and psoriasis vulgaris (PsV) are considered to be Th2 and Th1 type disease, respectively. The IL-12 p40 subunit gene (IL12B) is located at chromosome 5q31-33 and linkage findings of AD on 5q31 were reported. Recently single nucleotide polymorphism (SNP) (1188A/C) of IL12B has been reported. In function, it has been reported that this SNP is associated with IL12B mRNA expression levels. To learn whether this SNP is associated with susceptibility to AD or PsV, we investigated the genotype and allele frequencies of the SNP in AD patients, in PsV patients and in controls, examining 164 AD patients, 143 PsV patients and 100 healthy individuals in Japanese population. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. The A allele was decreased in AD patients (40.9%, p = 0.031) and increased in PsV patients (60.1%, p = 0.035) compared with controls (50.5%). This suggests that IL12B SNP is associated with susceptibility to AD and PsV, presumably by affecting the Th1/Th2 balance.     

儿童特应性皮炎IL-18基因启动子多态性与相关性研究

目的 检测儿童特应性皮炎患者外周血DNA中IL-18基因第2外显子上游启动子1第137和第607位点多态性，探讨其与儿童特应性皮炎发病的相关性。方法 从82例重庆汉族儿童特应性皮炎患者及健康对照组100例的抗凝血中提取DNA，用序列特异性引物PCR扩增技术（PCR-SSP）及PCR产物直接测序法鉴定基因类型，对结果进行统计学分析处理。结果 IL-18基因第2外显子的第137位点核苷酸存在G、C二态性，可表现为GG纯合、CC纯合、GC杂合三种基因型；第607位点核苷酸存在C、A二态性，可表现为CC纯合、AA纯合、CA杂合三种基因型。IL-18-137G/C基因型分布在患者组和对照组间差异有统计学意义，患者组137C等位基因频率显著高于对照组（χ2 = 4.54，P = 0.033），137C等位基因在重度组中分布频率显著高于轻度组（χ2 = 3.93，P < 0.05）；IL-18-607位点等位基因频率在轻度、中度、重度组及对照组之间分布差异无统计学意义（P > 0.05）；IL-18-137G/C位点C等位基因在病例与对照组比较，优势比OR = 1.76，137G/C基因型的优势比OR = 2.33。结论 儿童IL-18基因第2外显子上游启动子1第137和第607位点存在单核苷酸多态性，IL-18-137G/C是特应性皮炎患儿的候选易感基因。     

Lack of association between the promoter polymorphisms at positions -308 and -238 of the tumor necrosis factor alpha gene and psoriasis vulgaris in Japanese patients

BACKGROUND: Psoriasis features an increased level and activity of tumor necrosis factor alpha (TNF-alpha). The TNF-alpha gene has single nucleotide polymorphisms (SNPs) at positions -308 (-308G>A) and -238 (-238G>A) in the promoter region, and the -238G>A SNP has been reported to be associated with psoriasis vulgaris (PV) and psoriatic arthritis in Caucasians. OBJECTIVE: To examine whether these SNPs are associated with susceptibility to PV in Japanese patients, we investigated the genotype and allele frequencies at each SNP in Japanese PV patients and in controls. METHODS: We examined 163 PV patients and 96 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: No significant association between the genotypes or alleles of these SNPs and susceptibility to PV was observed. CONCLUSION: These SNPs themselves are not associated with susceptibility to PV in the Japanese.     

Determination of thymus and activation-regulated chemokine (TARC)-contents in scales of atopic dermatitis

BACKGROUND: Thymus and activation-regulated chemokine (TARC) is a cytokine which selectively controls the migration of type 2-helper T lymphocytes into inflammatory lesions, and the serum level is strongly associated with disease severity of atopic dermatitis (AD). OBJECTIVE: To examine the role of TARC in the pathogenesis of AD, we determined TARC-contents in the scales obtained from lesional skin of the patients with AD. RESULTS: High amount of TARC was detected in the scales of lesional skin obtained from the patients with AD, and the amount was well correlated with the serum IgE levels but not with the blood eosinophil counts. The TARC-content in the lesional scales was not correlated with a-431C/T polymorphism of TARC promotor gene, suggesting other regulating mechanisms in TARC production in the lesion. CONCLUSION: High amount of TARC is produced in the kesion of AD, and analysis of cytokine content in lesional scales may provide some tools to clarify the pathogenesis of AD.     

CD40基因多态性及血清水平与系统性红斑狼疮发病机制的相关研究

目的 探讨CD40基因单核苷酸多态性（SNP）及其单倍型与SLE易感性的相关性,分析CD40基因型及血清水平与系统性红斑狼疮（SLE）的相关性。 方法 单碱基延伸的PCR技术（PCR-SBE）和DNA测序法分析205例SLE患者和220例健康对照CD40基因rs1883832 C/T、 rs13040307 C/T、rs752118 C/T 和rs3765459 G/A的多态性,同时用ELISA检测血清CD40水平。 结果 与健康对照组相比,SLE组血清CD40水平显著增高（P < 0.05）。SLE组与健康对照组CD40基因rs1883832 C/T位点基因型和等位基因频率比较,差异有统计学意义（P < 0.01）。等位基因频率的相对风险分析后发现,携带有rs1883832 T等位基因的受试者患有SLE的风险是rs1883832 C等位基因的1.517倍（OR = 1.517,95% CI 1.157 ~ 1.990,P = 0.003）;携带rs1883832 T等位基因的SLE患者血清CD40水平与不携带者相比,结果显著增高（P < 0.01）。通过联合基因型分析发现,SLE组中携带单倍型TCCA的患者较健康对照组显著增加了发病的风险（OR = 2.322,95% CI 1.181 ~ 4.564,P = 0.012）。 结论 CD40基因rs1883832 C/T多态性和TCCA单倍型与SLE的发病有相关性,其中rs1883832 T等位基因可能是SLE的遗传易感基因。     

Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients

CCR4, a member of the CC chemokine receptor family, is believed to play an important role in the pathogenesis of atopic dermatitis. To examine whether CCR4 single nucleotide polymorphism (SNP) is associated with susceptibility to atopic dermatitis, we investigated the allele and genotype frequencies of C1014T SNP of CCR4 in 198 Japanese patients with atopic dermatitis and controls by a PCR-restriction fragment length polymorphism method. There was no significant difference in allele or genotype frequencies between patients with atopic dermatitis and controls. Serum IgE levels and peripheral blood eosinophil counts were not significantly different among genotypes. There was also no significant difference in allele or genotype frequencies between the patient subgroup with and without asthma, with mild or moderate disease, with and without family history of atopic dermatitis, or with and without family history of atopic disorders. C1014T SNP of CCR4 does not appear to be associated with susceptibility to atopic dermatitis in Japanese patients.     

广西壮族、汉族系统性红斑狼疮与Toll样受体9基因多态性研究

目的 探讨TLR9单核苷酸多态性与广西系统性红斑狼疮（SLE）患者发病的相关性,以及其在壮族、汉两个民族间的差异。 方法 聚合酶链反应-限制性酶切技术、聚合酶链反应-限制性片段长度多态性分析技术（PCR-RFLP）对97例广西SLE患者和202例广西健康对照者的TLR9基因多态性进行检测,分析其基因型和等位基因频率与SLE部分临床实验室指标的关联性,并比较两民族间的差异。 结果 TLR9 rs352140CC、CT、TT基因型频率在汉族SLE组与汉族对照组中分别为42.9%、41.1%、16.1%和38.3%、55.8%、5.8%,差异有统计学意义（P < 0.05）,其C、T等位基因频率差异无统计学意义（P > 0.05）。TLR9rs352140 C/T基因型频率和等位基因频率在壮族SLE组与壮族健康对照组间、壮族SLE组与汉族SLE组间差异无统计学意义（均P > 0.05）。TLR9 rs352140TT基因型频率在ds-DNA阳性组比阴性组高（P < 0.05）,而T等位基因频率在两组间差异无统计学意义（P > 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在SLEDAI ≥ 9组比SLEDAI < 9组高,差异有统计学意义（均P < 0.05）。TLR9 rs352140TT基因型频率和T等位基因的频率在ANA阳性组与阴性组间差异无统计学意义（均P > 0.05）。 结论 TLR9 rs352140基因多态性可能与广西汉族人SLE的易感性有关, TLR9基因多态性与部分SLE指标可能具有相关性。     

A novel single-nucleotide polymorphism of the Fcgamma receptor IIIa gene is associated with genetic susceptibility to systemic lupus erythematosus in Chinese populations: a family-based association study

BACKGROUND: Systemic lupus erytematosus (SLE) is characterized by the presence of various autoantibodies and the deposition of immune complexes which are cleared by Fcgamma receptors. OBJECTIVES: Family-based association analysis was performed to investigate whether the FCGR3A-72S/R and FCGR3A-270T/R polymorphisms are risk factors for SLE in a Chinese population. METHODS: In total, 119 patients with SLE from 95 nuclear families, aged 14-78 years, who met the American College of Rheumatology 1997 criteria were recruited, as were 316 family members of these patients. We studied two single-nucleotide polymorphisms (SNPs) encoding nonsynonymous substitution in the FCGR3A gene with respect to genetic susceptibility to SLE in a collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR restriction fragment length polymorphism. RESULTS: Our results showed that FCGR3A-72R/S have an excess of transmission of the R allele from heterozygous parents to affected offspring (transmission disequilibrium test chi2 = 9.30, P = 0.0032). Univariate (single-marker) family-based association tests demonstrated that a variant allele at SNP rs403016 of the FCGR3A gene was significantly associated with genetic susceptibility to SLE (exon 3, Z = 2.5444, P = 0.01097) in an additive model. The R and S allele frequencies were 39.4% and 60.6%, respectively. The frequencies of FCGR3A 72R/R, R/S and SS genotypes were 9.1%, 60.6% and 30.3%, respectively. However, the FCGR3A-270T/S SNP was not found in this Chinese population. CONCLUSION: This study suggests a linkage disequilibrium of the FCGR3A-72R/S SNP with SLE, and supports the notion that a novel polymorphism of the FCGR3A-72R/S SNP is associated with genetic susceptibility to SLE in Chinese populations.     

Brain-derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients

Background  Brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of atopic dermatitis (AD). Whether BDNF gene polymorphisms are associated with Chinese AD remains totally unknown.
Objective  The aim is to determine if BDNF gene C270T and G196A polymorphisms are associated with Chinese AD, and analyse the clinical relevance of BDNF gene polymorphisms and BDNF serum levels.
Methods  We conducted a case-control association analysis (160 patients and 169 controls) in Northern Chinese subjects. Genotyping was performed by restriction fragment length polymorphism, and serum levels of BDNF were measured using enzyme-linked immunosorbent assay.
Results  For C270T, there were significant differences in C/T genotype distribution ( P  = 0.003) and T allele frequencies ( P  = 0.004) between AD patients and controls in the whole dataset. Higher C/T genotype frequencies were found in male AD (10.6% vs. 1.1%, P  = 0.018) and in intrinsic AD (IAD; 15.79% vs. 2.91%, P  = 0.008). No association between G196A polymorphism and AD was observed in the whole cohort, while A allele was much more frequent in AD patients with atopy in first-degree relatives (65.8% vs. 34.2%, P  = 0.038). Serum BDNF levels were correlated with IAD severity as measured by Scoring Atopic Dermatitis index ( r  = 0.576, P  < 0.001).
Conclusion  T allele in C270T may be a risk factor for AD, especially in IAD and male AD. A allele in G196A may be a risk factor in AD patients with atopy in first-degree relatives. Serum BDNF levels were correlated with the severity of IAD.     

Lack of association between the G-2548A polymorphism of the leptin gene and psoriasis in a Turkish population

BACKGROUND: Psoriasis is a multifactorial disease in which genetic and inflammatory factors play important roles. Leptin is classified as a cytokine and plays an important role in the regulation of the T-helper response. A common polymorphism in the promoter of the human leptin gene (G-2548A) may have a role in the pathogenesis of psoriasis. AIM: To investigate the association between psoriasis and leptin gene polymorphism (G-2548A). METHODS: The study involved 109 patients with psoriasis and 125 healthy controls. Analyses of G-2548A polymorphism of the leptin gene were made by the polymerase chain reaction-restriction fragment length polymorphism technique. The genotypes (GG, GA, and AA of leptin gene G-2548A) and alleles (G and A) were scored and the frequencies were estimated. The frequencies of alleles and genotypes in patients and controls were compared. The relationship between leptin gene polymorphism and the clinical features of the patients was analyzed. RESULTS: Both genotype [odds ratio (OR), 0.921; 95% confidence interval (CI), 0.501-1.694; P = 0.792] and allele (OR, 0.864; 95% CI, 0.600-1.242; P = 0.429) frequencies were not significantly different between patient and control groups. In addition, there was no significant association between genotype and allele frequencies and the clinical characteristics of psoriasis. CONCLUSION: In this case-control study, no evidence of association between the G-2548A variant of the leptin gene and psoriasis was found.     

雌激素受体-α基因多态性与白癜风相关性研究

目的探讨雌激素受体-α(ER-α)基因多态性与白癜风的相关性。方法应用PCR-RFLP分析技术,检测690例汉族白癜风患者和700例汉族对照者ER-α基因内含子1PvuⅡT/C和XbaIA/G酶切位点基因多态性。结果白癜风组与对照组之间C/T基因型频率(P=0.000)差别有显著性意义,其C等位基因频率亦明显高于对照组(P=0.000,OR1.33,95%CI1.14~1.51);女性患者C/T基因型频率(P=0.001)、C等位基因频率(P=0.002,OR1.41,95%CI1.13~1.75)亦明显高于女性对照组;男性患者和男性对照组C等位基因频率(P=0.043,OR1.25,95%CI1.01~1.56)差别有显著性意义;ER-α基因内含子1XbaⅠA/G酶切多态性男性患者G等位基因频率(P=0.040,OR1.32,95%CI1.01~1.71)明显高于男性对照组;其余各组间差别无显著性意义(P>0.05)。结论ER-α基因PvuII酶切多态性与白癜风存在相关性,携带C等位基因的女性患者更易患白癜风。XbaI酶切多态性可能与男性白癜风患者之间存在相关性。提示ER-α可能是白癜风患者易感性的备选因素。     

Psoriasis vulgaris in Chinese individuals is associated with PSORS1C3 and CDSN genes

BACKGROUND: Besides the HLA-Cw*0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The -79C, -26C and +246A alleles of the PSORS1C3 gene, the CDSN*971T allele, CDSN*TTC (619T-1236T-1243C) and CDSN*5 (619T-1240G-1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris. OBJECTIVES: We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. METHODS: We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA-Cw*0602, alpha-helix coiled-coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence-based typing method. RESULTS: The PSORS1C3*582A allele, an SNP in the 3'-untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early-onset psoriasis vulgaris (22.3% vs. 6.9%, odds ratio = 3.87, P(c) =0.0000072). The frequencies of CDSN*TTC and CDSN*971T were also significantly increased in patients with early-onset psoriasis vulgaris. Moreover, PSORS1C3*582A, SNP n.9*C, Cw*0602 and HCR*WWCC were in near complete linkage disequilibrium (LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9*C-Cw*0602-PSORS1C3*582A-HCR*WWCC was a major susceptibility haplotype in patients with early-onset psoriasis vulgaris (P < 10(-7)) and this risk haplotype also carried CDSN*TTC and CDSN*971T. CONCLUSIONS: The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.     

中间丝聚合蛋白基因多态性与特应性皮炎发病及临床表型的相关性

目的 探讨中间丝聚合蛋白(FLG)基因多态性与特应性皮炎(AD)发病及临床表型的相关性.方法 采用问卷调查的形式收集261例AD患者伴发过敏性鼻炎、哮喘病史和疾病严重度评分等资料,对部分患者进行混合食物过敏原和混合吸人性过敏原筛选、血清总IgE抗体和嗜酸性粒细胞阳离子蛋白水平检测.采用重叠PCR和DNA测序法对上述AD患者和276例健康对照FLG基因3号外显子17个多态性位点(R444G、T454A、P478S、H519N、D836D、S1482Y、A1805V、R1891Q、1961Q、S2166S、Y2194H、H2330H、D2339N、S2366T、E2398Q、K2444E、E2652D)进行基因分型.结果 二项逻辑回归分析和卡方检验未发现17种FLG多态位点与AD发病相关(均P＞0.05).H519N与AD伴发哮喘相关(x2=8.680,P=0.011),AA基因型可增加AD患者发生哮喘的风险(P=0.004,OR=1.061,95％ CI 1.016 ～ 1.109).S2366T和K2444E与AD患者食物敏感相关(x2值分别为6.520和6.121,P值分别为0.038和0.047),S2366T的GG+ GC基因型(P=0.012,OR=1.396,95％CI 1.054～1.849)和G等位基因(P=0.037,OR=1.350,95％CI 1.008～ 1.807)可提高AD患者食物敏感的风险.K2444E的AA+ AG基因型(P=0.013,OR=1.393,95％ CI 1.049 ～ 1.850)和G等位基因(P=0.028,OR=1.380,95％ CI 1.025 ～ 1.857)可提高AD患者食物敏感的风险.结论 中国汉族人群FLG基因多态性可能是一些AD相关临床表型的危险因素,H519N可能与AD伴发哮喘相关,S2366T和K2444E则可能与AD伴食物敏感相关.     

Tumor necrosis factor-alpha and interferon-gamma polymorphisms contribute to susceptibility to oral lichen planus

Most lymphocytes in the lamina propria of oral lichen planus (OLP) lesions express and secrete interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), whereas they do not secret interleukin-4 and -10 or transforming growth factor-beta. We analyzed whether the polymorphisms of several cytokines may influence the susceptibility to OLP. Cytokine typing was performed by a sequence-specific PCR assay. Thirteen cytokine genes with 22 single-nucleotide polymorphisms were studied. IFN-gamma UTR 5644 genotype frequencies showed a significant increase in number of T/T homozygotes in OLP patients compared with controls (40.9 vs. 22.9%; p=0.0022). Moreover, in OLP patients, the frequency of the -308A TNF-alpha allele was higher than in the controls (21.6 vs. 9.3%; p < 0.05) causing a significantly increased frequency of the genotype G/A in OLP (43.2 vs. 14.3%; p=0.0002). Because in patients with mucocutaneous lichen planus (LP), the frequency of the -308A TNF-alpha allele was more than double the values in the pure OLP patients (40.9 vs. 15.1%; p=0.003), the -308G/A TNF-alpha genotype showed a significantly higher frequency in patients with mucocutaneous LP than in patients with pure OLP (81.8 vs. 30.3%, p=0.003). In conclusion, we suggest that genetic polymorphism of the first intron of the promoter gene of IFN-gamma may be an important risk factor to develop oral lesions of LP, whereas an increase in the frequency of -308A TNF-alpha allele may best contribute to the development of additional skin involvement.     

Single nucleotide polymorphisms of Ficolin 2 gene in Behçet's disease

BACKGROUND: Genetic susceptibility to Beh?et's disease (BD) is well documented for HLA-B51 positivity. However, BD is not a simple hereditary disease and it is exaggerated by exogenous stimuli such as microorganisms' infections. Ficolin 2 is a lectin that binds to the surface of microbial cells and kills microbial cells through the activation of complement system. Novel single nucleotide polymorphisms (SNPs) of human Ficolin 2 gene (FCN2 gene) have been recently identified in Caucasian people. OBJECTIVE: The aim of the study was to elucidate the contribution of FCN2 gene in the pathogenesis of BD. METHODS: The frequencies of genotypes and alleles of FCN2 gene SNPs in the promoter regions (-987, -602, -557, -64, -4) and exon 8 (+6359, +6424) were examined in 83 patients with BD and 64 healthy controls by genotyping with a DNA sequencing method. RESULTS: There were no significant differences in genotype and allele frequencies of FCN2 gene SNPs between BD patients and healthy controls. No significant differences in genotype and allele frequencies of FCN2 gene SNPs were detected among different clinical subgroups in BD patients. Significant differences in allele frequencies of FCN gene SNPs at both -557 and -64 sites in the promoter regions were found between HLA-B51 positive groups and HLA-B51 negative groups of BD patients. CONCLUSION: The significant differences in allele frequencies of FCN2 gene SNPs in the promoter lesions (-557 and -64 sites) among HLA-B51 positive BD patients may reveal the possibility that ficolin may contribute to the innate immunity of BD among HLA-B51 haplotypes in BD patients.