Haplotype associations of the MHC with psoriasis vulgaris in Chinese Hans

Summary Haplotype associations of the major histocompatibility complex (MHC) with psoriasis vulgaris (PV) have been demonstrated in different racial or ethnic populations. The objective of this study was to demonstrate the different haplotype associations of the MHC in Chinese patients with psoriasis according to the type of onset and their sex. One hundred and thirty-eight patients with PV and 149 normal control subjects without psoriasis were typed for HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 by using the PCR with sequence-specific primers. The results showed: (i) HLA-A*26 (26.1% vs. 12.1%, Pc < 1 x 10(-5)), -B*27 (17.03% vs. 1.01%, Pc < 1 x 10(-7)), -Cw*0602 (15.58% vs. 5.03%, Pc < 1 x 10(-2)), -DQA1*0104 (19.93% vs. 9.40%, Pc < 1 x 10(-3)), -DQA1*0201 (22.40% vs. 10.74%, Pc < 1 x 10(-3)), -DQB1*0303 (18.12% vs. 9.73%, Pc < 1 x 10(-7)), and -DRB1*0701/02 (26.09% vs. 9.73%, Pc < 1 x 10(-7)) were significantly increased in PV patients, while HLA-B*57, -DQB1*0201 were slightly increased in PV patients. HLA-Cw*0304 (5.07% vs. 14.43%, Pc < 1 x 10(-3)), -DQA1*0501 (5.79% vs. 14.09%, Pc < 0.05) were found to be negatively associated with PV, but HLA-A*2 (2.54% vs. 6.38%, Pc < 0.5) was decreased in PV patients without statistical significance. (ii) HLA-A*26-B*27 [P < 0.0001, odds ratio (OR) = 48.38], -A*26-Cw*0602 (P < 0.0001, OR = 11.84), -B*27-Cw*0602 (P < 0.0001, OR = undefined), -DRB1*0701/02-B*27 (P < 0.0001, OR = 22.62), -DRB1*0701/02-DQA1*0104 (P < 0.0002, OR = 3.59), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 5.63), -DQA1*0201-DQB1*0303 (P < 0.0002, OR = 7.77), -A*26-B*27-Cw*0602 (P < 0.0004, OR = undefined), -A*26-DRB1*0701/02-DQA1*0201-DQB1*0303 (P < 0.01, OR = undefined) were identified as risk haplotypes for patients with PV in China. (iii) HLA-A*26 -B*27 (P < 0.0001, OR = 58.47), -DQA1*0201-DQB1*0303 (P < 0.0001, OR = 8.62), -DRB1*0701/02 -DQA1*0104 (P < 0.0002, OR = 4.13), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 6.68) and -A*26-DRB1*0701-DQA1*0201 -DQB1*0303 (P < 0.006, OR = undefined) were only significantly associated with type I psoriasis compared with controls, while others showed no differences in either type I or type II psoriasis. (iv) These associated haplotypes with PV were not different by sex, except that the frequency of DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 10.14) was higher in male patients with psoriasis. To summarize, this study demonstrated a differential association of HLA and identified some special risk haplotypes in Chinese patients with PV compared with other ethnic or racial populations.     

A new extended haplotype Cw*0602-B57-DRB1*0701-DQA1*0201-DQB1*0201 associated with psoriasis in the Croatian population

In this study, we have analysed the distribution of HLA class II alleles and the extended haplotype HLA-Cw-B-DRB1-DQA1-DQB1 in Croatian patients with type I and type II psoriasis by hybridization with specific oligonucleotide probes. Type I psoriasis showed a significant association with the DRB1*0701 [P < 0.00001; relative risk (RR) = 5.83], DQA1*0201 (P < 0.00001; RR = 6.12), DQB1*0201 (P = 0.0006; RR = 3.29) and DQB1*0303 alleles (P = 0.0008; RR = 7.51). A negative correlation with type I disease was observed for the DQA1*0102 allele (P = 0.002; RR = 0.26). Type II psoriasis did not show any association with any class II alleles. The extended haplotype HLA-Cw*0602-B57-DRB1*0701-DQA1*0201-DQB1*0201 was present at a significantly higher frequency in type I patients (P < 0.00001; RR = 7.72). However, this haplotype was not detected at all in patients with type II psoriasis. In conclusion, the extended haplotype HLA-Cw*0602-B57-DRB1*0701-DQA1*0201-DQB1*0201 is a risk haplotype for type I disease in the Croatian population. This particular haplotype has not been reported previously in association with psoriasis in any other ethnic groups.     

MHC haplotypic association in Chinese Han patients with vitiligo

BACKGROUND: Serological typing of the human leucocyte antigen (HLA) has shown discrepancies in HLA associations with vitiligo in different ethnic populations. OBJECTIVE: To evaluate the distributions of HLA at class I and II loci that may contribute to the genetic susceptibility of vitiligo patients in Chinese Hans population. METHODS: We analysed the allelic frequencies of HLA class I and II by using the polymerase chain reaction sequence-specific primer (PCR-SSP) method in 187 patients with vitiligo and 273 controls in Chinese Hans. The linkage disequilibrium was calculated from a 2 x 2 table. RESULTS: Two-locus haplotypes including HLA-A25-B13, HLA-A25-B27, HLA-A25-Cw*0602, HLA-A25-DQA1*0302, HLA-A25-DQA1*0601, HLA-A25-DQB1*0303, HLA-B13-Cw*0602, HLA-B13-DQA1*0302, HLA-B13-DQA1*0601, HLA-B27-Cw*0602, HLA-B27-DQA1*0302, HLA-B27-DQA1*0601, HLA-B27-DQB1*0303, HLA-B27-DQB1*0503, HLA-Cw*0602-DQA1*0302, HLA-Cw*0602-DQA1*0601, HLA-Cw*0602-DQB1*0303, HLA-Cw*0602-DQB1*0503 and HLA-DQA1*0302-DQB1*0503 were associated with all types of vitiligo in Chinese Hans. The extended haplotypes HLA-A25-B13-Cw*0602, HLA-A25-B27-Cw*0602, HLA-DQA1*0302-DQB1*0303-Cw*0602 and HLA-B13-DQB1*0303-Cw*0602 were found to be associated with all types of vitiligo in Chinese Hans, whereas the frequency of HLA-A25-Cw*0602-DQA1*0302 was significantly increased in generalized vitiligo but not in localized vitiligo. The frequencies of HLA-A25-DQA1*0302-DQB1*0503 and HLA-A30-DQA1*0302-DQB1*0303 were higher in childhood vitiligo than in adult vitiligo, and the frequency of HLA-A25-B13-DQB1*0303-Cw*0602 was shown to be associated with adult vitiligo but not childhood vitiligo. CONCLUSION: This study demonstrates not only the differential association between HLA markers and types of vitiligo according to distribution or age at onset but also newly found high-risk haplotypes in Chinese vitiligo patients.     

Haplotype associations of the major histocompatibility complex with psoriasis in Northeastern Thais

BACKGROUND: To evaluate the distributions of the human leukocyte antigen (HLA) at class I and II loci that may contribute to the genetic susceptibility to psoriasis patients in the north-eastern Thai population. MATERIALS AND METHODS: We analyzed the allelic frequencies of HLA class I and II by using the polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique and polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP), respectively, in 140 north-eastern Thais with psoriasis that were sudivided into two groups: one with age at onset < 40 years (type I psoriasis; 95 cases) and the other with age at onset > 40 years (type II psoriasis; 45 cases). Three hundred healthy unrelated north-eastern Thais were used as controls. RESULTS: HLA-A*01, -A*0207, -A*30, -B*08, -B*13, -B*4601, -B*57, -Cw*01, -Cw*0602, and -DRB1*07 were positively associated with type I psoriasis, whereas HLA-A*24, -A*33, and -Cw*04 were negatively associated with type I psoriasis with statistical significance when compared to the controls. The Cw*0602 allele showed the strongest correlation with this type. In addition, the frequencies of HLA-A*0207, -A*30, -Cw*01, and -DRB1*1401 were significantly increased in type II psoriasis. HLA-A*207, -B*4601, -Cw*01, -DRB1*09, -DQB1*0303 (AH46.1), HLA-A*01-B*57-Cw*0602-DRB1*07-DQB1*0303 (AH57.1), and HLA-A*30, -B*13, -Cw*0602, -DRB1*07, and -DQB1*02 (AH13.1) were identified as high-risk major histocompatibility complex (MHC) halotypes for psoriasis patients in the early onset group in north-eastern Thais. CONCLUSIONS: This study demonstrates not only the differential association between HLA markers and types of psoriasis according to age at onset, but also a newly found high-risk and a protective haplotype in Thai psoriasis patients.     

Association of HLA haplotype with alopecia areata in Chinese Hans

BACKGROUND: Some studies have shown discrepancies in human leucocyte antigen (HLA) associated with alopecia areata (AA) between different ethnic populations. OBJECTIVE: To investigate whether HLA-I, -DQA1 and -DQB1 alleles and the HLA haplotype are associated with AA, and the correlation between the HLA haplotype profile, age of onset and severity of AA in Chinese Hans. METHODS: The polymerase chain reaction-sequence specific primer (PCR-SSP) method was used to analyse the frequencies of HLA class I, -DQA1 and -DQB1 alleles in 192 patients with AA and 252 controls in Chinese Hans. The linkage disequilibrium was calculated using the 2 x 2 table. RESULTS: The 24 two-locus haplotypes [including A*02-B*18, A*02-B*27, A*02-B*52, A*02-Cw*0704, A*02-DQA1*0104, A*02-DQB1*0604, A*02-DQB1*0606, B*18-Cw*0704, B*18-DQA1*0104, B*18-DQA1*0302, B*18-DQB1*0606, B*27-Cw*0704, B*27-DQA1*0104, B*27-DQA1*0302, B*52-Cw*0704, B*52-DQA1*0104, B*52-DQA1*0302, B52-DQB1*0606, Cw*0704-DQA1*0104, Cw*0704-DQA1*0302, Cw*0704-DQB1*0606, DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, DQA1*0302-DQB1*0606 (P<0.05)] were associated with AA, while eight extended haplotypes (A*02-B*18-DQA1*0104, A*02-B*27-DQA1*0104, A*02-B*52-DQA1*0104, A*02-B*52-DQA1*0302, A*02-B*52-DQB1*0606, B*52-Cw*0704-DQA1*0104, B*52-Cw*0704-DQA1*0302, A*02-B*52-DQA1*0302-DQB1*0606) were found to be related to AA in Chinese Hans. Through stratified analysis, we found that the extended haplotype B*52-Cw*0704-DQA1*0302 was related to early onset of AA, and no haplotype was only associated with severe AA. CONCLUSION: This is the first detailed report to elucidate HLA haplotypes associated with AA and that demonstrates the significant HLA haplotypes in Chinese Hans AA. The haplotype B*52-Cw*0704-DQA1*0302 was identified to be related to early onset of AA. Our results provide some information for future research on predisposing genes in HLA regions in Chinese Hans.     

Association of HLA class I alleles with psoriasis vulgaris in southeastern Chinese Hans

BACKGROUND: Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. OBJECTIVE: To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. METHODS: We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. RESULTS: The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, Pc<0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, Pc<0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, Pc<0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, Pc<0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, Pc<0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset <35 y). CONCLUSION: This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.     

Comparison of clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population

HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of K?bner's phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.     

Analysis of HLA antigens in Croatian patients with psoriasis

In common with most autoimmune diseases, psoriasis is associated with some HLA antigens. We studied the distribution of HLA antigens in Croatian patients with psoriasis: 108 patients were divided into groups according to family history and age of disease onset. HLA antigens were analyzed serologically and HLA-C alleles were analyzed using polymerase chain reaction. We found significant increases in HLA-A2, -B17, -B37 and -B13 antigens and highly significant increases in HLA-Cw*0602 and DR7 antigens in psoriatic patients compared with controls. Patients with type I psoriasis (early onset, positive family history) showed highly significant associations with Cw*0602 [p < 0.00001; relative risk (RR) = 14.45] and DR7 (p < 0.00001; RR = 15.09) antigens. Patients with type II psoriasis (late onset, no family history) had a significant association with Cw*03 antigen (p = 0.008; RR = 0.17). In conclusion, HLA-B13, -B17, Cw*0602 and -DR7 antigens are associated with a significant risk of psoriasis in the Croatian population and the Cw*0602 allele has the strongest association, especially for type I psoriasis.     

内蒙古蒙古族寻常性银屑病与HLA-Cw*0602,-DQB1等位基因的相关性

目的探讨内蒙古蒙古族寻常性银屑病与HLA-Cw*0602,-DQB1等位基因的关联性。方法利用序列特异性引物-聚合酶链反应(PCR-SSP)分型技术,对蒙古族寻常性银屑病患者65例及对照组正常蒙古族60例样本进行分型检测并比较分析。结果①寻常性银屑病患者组HLA-Cw*0602,-DQB1*0201等位基因频率较对照组明显升高,差异有统计学意义(P0.05);②HLA-Cw*0602,-DQB1*0201在Ⅰ型及家族史阳性银屑病患者中显著升高(P0.05);③HLA-DQB1*0301在患者组中有显著下降(P0.05)。结论①HLA-Cw*0602及-DQB1*0201可能是内蒙古地区蒙古族寻常性银屑病的易感基因;有家族史和无家族史银屑病患者可能存在遗传背景上的差异。     

Genetic polymorphisms of the HCR gene and a genomic segment in close proximity to HLA-C are associated with patients with psoriasis in Taiwan

BACKGROUND: Although psoriasis vulgaris (PV) is strongly associated with HLA-Cw*0602, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in PV susceptibility. The alpha-helix coiled-coil rod homologue (HCR) gene, located 110 kb telomeric to the HLA-C locus, is presumed to be one of the PV candidate genes. Recently, a 10-kb genomic segment, centromeric to HLA-C, defined by two new single nucleotide polymorphisms (SNPs) n.7*A and n.9*C, was found to have a stronger association with psoriasis than the HCR gene. Until now, no study of the association of the HCR gene, SNPs n.7, and n.9 has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the HCR gene, SNPs n.7*A, and n.9*C were associated with an increased risk of psoriasis in Chinese patients. METHODS: Using direct sequencing of the HCR gene and the genomic region containing SNPs n.7 and n.9, we investigated the HCR gene, SNPs n.7, and n.9 for disease association in 115 Chinese patients with psoriasis and 103 control subjects. The HCR SNPs were confirmed by denaturing high performance liquid chromatography. Genotyping for HLA-Cw*0602 was also carried out using sequence-based typing. RESULTS: We observed a different allelic distribution between patient and control groups at nucleotide positions 386, 404, 1802 and 2406 of the HCR gene, and SNPs n.7, and n.9. The associations were much stronger in early onset PV patients (for HCR-386*T and HCR-404*T, odds ratio = 5.63, Pc < 0.0001). The HLA-Cw*0602 also displayed a similar association with PV (odds ratio = 5.4, Pc < 0.0001). Moreover, SNP n.7*A, SNP n.9*C, Cw*0602, HCR-386*T, HCR-404*T and HCR-1802*T were in linkage disequilibrium with each other. Haplotype-based association analysis showed SNP n.7*A-SNP n.9*C-Cw*0602-HCR-386*T-HCR-404*T-HCR-1802*T-HCR-2406*G as a major susceptibility haplotype in this Chinese population (for early onset patients, odds ratio = 5.15, Pc < 0.0001). CONCLUSIONS: Our results indicate that the HCR gene, SNP n.7*A, and SNP n.9*C as well as Cw*0602 are major susceptibility markers for psoriasis in Chinese patients.     

Genetics of psoriasis

Abstract Non-pustular psoriasis consists of two disease subtypes, type I and type II, which demonstrate distinct characteristics. Firstly the disease presents in different decades of life, in type I before the age of 40 years and later in type II. Secondly, contrasting frequencies of HLA alleles are found: type I patients express predominantly HLA-Cw6, -B57, and -DR7, whereas in type II patients HLA-Cw2 is overrepresented. Finally, familial inheritance is found in type I but not in type II psoriasis. The study of concomitant diseases in psoriasis contributes to deciphering the distinct patterns of the disease. Defence against invading microorganisms seems better developed in psoriatics than in controls. This evolutionary benefit may have caused the overall high incidence of psoriasis of 2%. Psoriasis is a multifactorial and heterogenetically inherited disease. The heterogeneity is evident by the diversity of genetically linked markers. The multifactorial component results from the observation of external trigger mechanisms, such as the Koebner phenomenon, stress and the intake of certain drugs. Twin studies have shown that environmental factors contribute to the onset of the disease. In type I psoriasis, special extended haplotypes such as EH57.1 (HLA-Cw6-B57-DRB1*0701-DQA1*0201-DQBl*0303) and EH65.1 (HLA-Cw8-B65-DRB1*0102-DQB1*0501) have been found to be increased. The application of microsatellite techniques has identified distinct positions on several chromosomes at which putative psoriasis genes may be located. Disease susceptibility genes are thought to be present on chromosomes 4q, 6p, 16q, 17q and 20p. Moreover, on chromosome 1q, genes regulating epidermal differentiation have been identified. Linkage to this area has been proposed. Furthermore, psoriasis gene loci on chromosomes 2, 8 and 20 have been suggested. Received: 19 May 1998     

蒙古族寻常性银屑病与HLA-Cw及DRB1位点相关性研究

【摘要】 目的 探讨蒙古族人群寻常性银屑病与HLA-Cw 及DRB1等位基因的相关性,为银屑病病因学研究提供依据。方法 序列特异性引物聚合酶链反应（PCR-SSP）对蒙古族寻常性银屑病患者81例及正常蒙古族100例进行HLA-Cw及DRB1位点的等位基因进行分型。结果 银屑病组HLA- Cw*06,DRB1*07等位基因频率显著高于健康对照组,HLA- Cw*04、DRB1*04等位基因频率显著低于健康对照组（Pc ＜ 0.05或0.01）。在发病年龄 ＜ 40岁银屑病及家族史阴性患者中HLA- Cw*06、DRB1*07等位基因频率显著高于健康对照组,而HLA- Cw*04、DRB1*04显著低于健康对照组（Pc ＜ 0.05）。在发病年龄≥ 40岁的银屑病及家族史阳性患者中只有HLA- Cw*06等位基因频率显著高于健康对照组（Pc ＜ 0.05）。结论 HLA- Cw*06、DRB1*07等位基因可能是内蒙古地区蒙古族人群寻常性银屑病的易感基因。HLA- Cw*04、DRB1*04等位基因可能是内蒙古地区蒙古族人群寻常性银屑病发病的保护因子。HLA- DRB1*07可能是发病年龄 ＜ 40岁的银屑病的易感基因,而HLA- Cw*04、DRB1*04则可能是发病年龄 ＜ 40岁银屑病的保护因子。     

HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to psoriasis vulgaris in Chinese Han

BACKGROUND: Psoriasis vulgaris is a chronic skin disorder characterized by infiltration of inflammatory elements, keratinocyte hyperproliferation and altered differentiation. Although the pathogenesis of psoriasis is not fully understood, there is solid evidence of a susceptibility locus in the human leukocyte antigen (HLA) region. OBJECTIVES: To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to psoriasis vulgaris in Chinese Han. PATIENTS AND METHODS: The polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyse the distribution of HLA-DQA1 and DQB1 alleles in 189 patients with psoriasis and 273 healthy controls. RESULTS: The HLA-DQA1*0104 (OR = 2.33, P = 0.0001154, Pc = 2.0 x 10-3), DQA1*0201 (OR = 3.36, P < 1.0 x 10-7, Pc < 1.0 x 10-6), DQB1*0201 (OR = 1.64, P = 0.0192, Pc > 0.05) and DQB1*0303 (OR = 1.55, P = 0.0377, Pc > 0.05) alleles were more prevalent in patients with psoriasis vulgaris than in controls, and HLA-DQA1*0501 (OR = 0.30, P = 0.0000039, Pc < 4.0 x 10-5) alleles were less prevalent. The HLA-DQA1*0104 (OR = 2.42, P = 0.0001159, Pc < 2.0 x 10-3), DQA1*0201 (OR = 3.74, P < 1.0 x 10-7, Pc < 1.0 x 10-6) and DQA1*0501 (OR = 0.30, P = 0.0000374, Pc < 4.0 x 10-4) alleles were only associated with type I psoriasis. HLA-DQA1*0104 and DQA1*0201 were more prevalent in patients with or without a family history of psoriasis. However, the DQA1*0501 allele was only more prevalent in patients without a family history of psoriasis. CONCLUSION: HLA-DQA1*0104 and DQA1*0201 alleles may be psoriasis susceptibility genes or may be in close linkage with the susceptibility genes. The HLA-DQA1*0501 allele seems to have a protective effect against the development of psoriasis vulgaris in Chinese Han. There may be a difference in genetic background between psoriasis patients with and without a family history of psoriasis.     

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.     

HLA—Cw＊0602与银屑病的关联研究

为研究HLACw*0602与DRB1*07两个基因在银屑病发病中的作用,采用PCRSSP基因分型方法,用一对引物扩增DRB1*073对引物扩增Cw*0602,扩增引物在含溴乙锭的1%琼脂糖凝胶电泳后,紫外灯下定型。结果,病人组和对照组Cw*0602阳性数分别为63.0%和7.4%,RR=21.3P<0.00001DRB1*07为54.3%和18.5%,RR=5.2P<0.0003。表明HLACw*0602是与银屑病关联的基因之一。     

内蒙古蒙古族和汉族人群白细胞介素12通路相关基因多态性与寻常型银屑病相关性及与HLA-Cw*0602交互作用研究

【摘要】 目的 探讨白细胞介素12（IL-12）通路相关基因多态性与内蒙古蒙古族和汉族寻常型银屑病患者的遗传相关性及与HLA-Cw*0602的交互作用。方法 收集2012年12月至2018年3月于内蒙古医科大学附属医院住院的寻常型银屑病患者1 409例为病例组,其中汉族1 030例,蒙古族379例,健康对照组1 483例,其中汉族965例,蒙古族518例。采集受试者外周静脉血5 ml提取DNA,选择位于IL-12B（rs2082412、rs2288831、rs3212227、rs3213094、rs7709212）、IL-23R（rs11209026、rs2201841、rs7530511）、IL-28RA（rs4649203）基因区域的9个单核苷酸多态性（SNP）,利用二代测序法进行基因多态性检测,利用序列特异性引物PCR对HLA-Cw*0602进行基因分型。利用PLINK1.07软件进行统计分析,χ2检验比较两组等位基因频率,并计算等位基因的相对危险度估计值比值比（OR）,R × C列联表卡方检验进行单倍型分析。结果 IL-12B基因rs2082412、rs2288831、rs3212227、rs3213094、rs7709212等位基因频率在汉族病例组显著低于汉族对照组（P < 0.005）;IL-12B基因rs3213094等位基因频率在蒙古族病例组显著低于蒙古族对照组（P < 0.005）。汉族和蒙古族病例组HLA-Cw*0602阳性率均显著高于相应民族对照组（P < 0.005）。分层分析显示,汉族HLA-Cw*0602阳性病例组IL-12B基因rs2082412、rs2288831、rs3212227、rs3213094、rs7709212等位基因频率显著低于汉族对照组（P < 0.005）,而阴性病例组与汉族对照组各等位基因频率差异无统计学意义（P > 0.05）。蒙古族HLA-Cw*0602阳性或阴性病例组各等位基因频率与相应对照组差异均无统计学意义（P > 0.005）。分析IL-12B基因区域的5个SNP构建单倍型,在汉族、蒙古族病例组和对照组中6个单倍型分析差异均无统计学意义（P > 0.005）。基于HLA-Cw*0602分层的IL-12B基因多态性单倍型分析,蒙古族、汉族7个单倍型无论HLA-Cw*0602阳性和阴性病例组及对照组中的频率差异无统计学意义（P > 0.005）。HLA-Cw*0602阳性和阴性蒙古族病例组和对照组,单倍型GATGT频率在两组间差异均无统计学意义（P > 0.05）。结论 IL-12通路相关基因多态性与内蒙古蒙古族、汉族人群寻常型银屑病具有相关性,且IL-12B与HLA-Cw*0602在寻常型银屑病发病过程中可能存在交互作用。     

HLA-Cw*0602 associates with a twofold higher prevalence of positive streptococcal throat swab at the onset of psoriasis: a case control study

Background

The influence of streptococcal infections in the pathogenesis of psoriasis is not yet understood. In vitro data suggest that streptococcal factors influence T-cell function in psoriasis in a HLA-dependent manner, but studies designed to measure the HLA-C/Streptococci interaction are lacking. In the present study, we hypothesized that there is a statistical interaction between the result of streptococcal throat cultures and the presence of the HLA-Cw*0602 allele in psoriasis patients.

Methods

We performed a case control study using the "Stockholm Psoriasis Cohort" consisting of patients consecutively recruited within 12 months of disease onset (Plaque psoriasis = 439, Guttate psoriasis = 143), matched to healthy controls (n = 454) randomly chosen from the Swedish Population Registry. All individuals underwent physical examination including throat swabs and DNA isolation for HLA-Cw*0602 genotyping. The prevalence of positive streptococcal throat swabs and HLA-Cw*0602 was compared between patients and controls and expressed as odds ratios with 95% confidence intervals. Associations were evaluated separately for guttate and plaque psoriasis by Fisher's exact test.

Results

Regardless of disease phenotype, the prevalence of positive streptococcal throat swabs in HLA-Cw*0602 positive patients was twice the prevalence among HLA-Cw*0602 negative patients (OR = 5.8 C.I. = 3.57–9.67, p < 0.001), while no difference was observed among Cw*0602 positive versus negative controls. The corresponding odds ratios for the guttate and plaque psoriasis phenotypes were 3.5 (CI = 1.5–8.7, p = 0.01) and 2.3 (CI = 1.0–5.1, p = 0.02) respectively.

Conclusion

These findings suggest that among HLA-Cw*0602 positive psoriasis patients, streptococci may contribute to the onset or exacerbation of the inflammatory process independent of the disease phenotype. However, studies on the functional interaction between HLA-C and streptococcal factors are needed.     

A study of PSORS1C1 gene polymorphisms in Chinese patients with psoriasis

BACKGROUND: Although genetic analyses have identified the HLA-Cw*0602 allele as the major risk allele for chronic plaque psoriasis in various ethnic groups, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in susceptibility to psoriasis. The psoriasis susceptibility 1 candidate 1 (PSORS1C1, formerly SEEK1) gene, located 127 kb telomeric to the HLA-C locus, is considered to be one of the potential candidate genes of psoriasis. Up to the present, no association study of the PSORS1C1 gene has been conducted on Chinese patients with psoriasis. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the PSORS1C1 gene were associated with an increased risk of psoriasis in Chinese patients. METHODS: We investigated the PSORS1C1 gene for disease association by direct sequencing of the PSORS1C1 gene in 143 Chinese patients with chronic plaque psoriasis and 188 control subjects. Genotyping for HLA-Cw*0602 and the alpha-helix coiled-coil rod homologue (C6orf18, formerly HCR) gene was also carried out using a sequence-based typing method. RESULTS: We identified 10 single nucleotide polymorphisms (SNPs) on the PSORS1C1 gene in our subjects; four of these SNPs cause amino acid change. We also detected poly(C) repeat variants from nucleotide positions 386-392 (poly(C)6-8). The poly(C) repeat polymorphisms cause a frame shift mutation. Another poly(C) repeat variant was also found at nucleotide positions 748-751. No significantly different allelic distributions of the PSORS1C1 SNPs or poly(C) repeat polymorphisms could be found between the patients with chronic plaque psoriasis and controls after correction for multiple testing. However, a significant increase of the Cw*0602 allele and tryptophan-tryptophan allele of the C6orf18 gene (HCR*WW) was found in patients with early onset psoriasis (21.9% vs. 4.8%, P < 10(-7)). Haplotype-based association analysis also showed a susceptibility haplotype carrying Cw*0602 and HCR*WW alleles in early onset Chinese patients. CONCLUSIONS: Our results indicate that the PSORS1C1 gene might not play an important role in the causation of chronic plaque psoriasis in Chinese people.     

Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients--an analysis of 1019 HLA-C- and HLA-B-typed patients

A major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined.     

Psoriasis patients who are homozygous for the HLA-Cw*0602 allele have a 2.5-fold increased risk of developing psoriasis compared with Cw6 heterozygotes

BACKGROUND: Psoriasis is strongly associated with certain human leucocyte-associated antigens, especially HLA-Cw*0602. Patients who are HLA-Cw*0602 positive have been reported to have more active disease and a younger age at disease onset than HLA-Cw6-negative patients. OBJECTIVES: To ascertain whether there are differences in the clinical features and relative risk between HLA-Cw*0602 homozygous and heterozygous psoriasis patients. METHODS: One thousand and six patients with chronic plaque psoriasis were evaluated clinically and HLA-C typed. In addition, 512 unrelated controls were typed for HLA-C. RESULTS: Of the patients 646 (64.2%) were HLA-Cw*0602 positive, and 68 (6.8%) were homozygous for this allele. Heterozygosity was associated with a relative risk of developing psoriasis of 8.9 compared with 23.1 for the Cw6 homozygous patients. The homozygous patients also had an earlier disease onset (mean 15.0 vs. 17.8 years, P = 0.04). However, the Cw6 homozygotes did not differ from the heterozygotes with respect to disease severity, guttate onset, distribution of plaques, nail changes or any other clinical parameter recorded. CONCLUSIONS: Homozygosity for the gene in the major histocompatibility complex region has a major additive impact on the risk of developing psoriasis and predisposes to an earlier disease onset, but does not have any marked influence on the phenotype or the severity of the disease.