HLA class Ⅱ alleles and risk for peripheral neuropathy in type 2 diabetes patients

The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. hTis study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 andP = 0.05 respectively). Also, patients with severe neurop-athy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our ifndings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.     

中国云南纳西族脑血管病患者载脂蛋白E基因的多态性

Currently it is not well known whether apolipoprotein E(ApoE) is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population.The present study detected and sequenced ApoE polymorphisms of 90 patients with cerebrovascular diseases(58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage),and 50 normal people of Naxi nationality from Yunnan province,China.The populations were used to analyze the relationship of ApoE polymorphisms with cerebral infarction and intracerebral hemorrhage.Results showed an association between ApoE gene polymorphism and the onset of cerebral infarction,and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction.However,there was no evidence of a relationship between the ApoE gene polymorphism and cerebral hemorrhage.     

急性缺血性脑血管病合并脑微出血的临床特征研究

目的 研究不同类型急性缺血性脑血管病患者合并脑微出血(CMB)的患病率及分级,并探讨其临床意义.方法 选择南方医科大学附属南方医院及广州中医药大学附属中山医院神经内科自2009年9月至2010年7月收治的急性缺血性脑血管病患者259例,其中动脉粥样硬化性血栓形成146例、心源性脑栓塞28例、小动脉性脑梗死50例、不明原因脑梗死19例,短暂性脑缺血发作(TIA)16例,同期体检者96例作为对照.常规行核磁共振T2梯度回波加权扫描(GRE-T2*WI),比较不同类型脑血管病患者CMB的患病率、分级以及初发性和复发性各亚型脑梗死患者CMB的患病率.结果 不同类型缺血性脑血管病患者CMB的患病率、分级均不同,差异有统计学意义(P＜0.05),除TIA外,脑梗死患者CMB的患病率均高于对照组,差异有统计学意义(P＜0.05),其中小动脉性脑梗死组最高(68.0%);复发性动脉粥样硬化性血栓形成患者CMB的患病率高于初发性患者,差异有统计学意义(P＜0.05).结论 CMB在各亚型脑梗死患者中患病率较高,其中在小血管性脑梗死中最高且严重;复发性动脉粥样硬化性血栓形成患者较初发性患者CMB的患病率高,提示CMB可能与缺血性卒中的复发有关.

Abstract：

Objective To study the prevalence and grade of cerebral microbleeds (CMB) among patients with different subtypes of acute ischemic cerebrovascular diseases, and investigate the clinical significance of CMB.Methods Consecutive 259 patients with acute ischemic cerebrovascular diseases, admitted to our hospitals from September 2009 to July 2010, were included; according to the stroke subtypes, these patients were classified into groups of atherothrombotic infarction (n=146),cardioembolic infarction (n=28), small artery infarction (n=50), infarction of unknown origin (n=19) and transient ischemia attack (TIA, n=16). The patients without cerebral vascular diseases were served as controls (n=96). The baseline data were registered and all patients were performed gradient echo-T2*weighted imaging (GRE-T2*WI); the prevalence and grade of CMB between each 2 different subtypes of acute ischemic cerebrovascular diseases were compared; the prevalence of CMB in patients with acute ischemic infarction for the first time and patients with recurrent cerebral infarction was compared.Results The prevalence and grade of CMB between each 2 different infarction subtypes varied with a statistical difference (P＜0.05). Apart from that of TIA group, the prevalence of all infarction groups was statistically higher than that of the controls (P＜0.05) with small artery infarction group being the highest (68.0%). The prevalence of CMB in patients with recurrent infarction was statistically higher than that in patients with primary infarction (P＜0.05).Conclusion The prevalence of CMB among different subtypes of infarction is high with the subtype of small artery infarction enjoying the highest rate; the prevalence of CMB in recurrent infarction goes higher as compared with that in primary infarction; the relapse of the cerebral infarction is possiblely related to the presence of CBMs.     

The study of low level laser irradiation therapy on brain infarction with SPECT

Objective: Effect of rCBF and brain function on ILIB treating brain infarction will be investigated by SPECT brain perfusion imaging. Method: 3 1 patients with brain infarction, 17 patients were treated by ILIB on standard pharmaceutial treatment. SPECT brain perfusion imaging was performed before and after ILIB therapy with comparison of oneself. They were quantified with BFCR% model effect during ILIB in 14 patients were observed. Result: ILIB 30 rnme SPECT showed the improvement of rCBF and cerebral function in 14 patients with brain infarction, and in 17 patients locus were prominence than mirror regions att er ILIB therapy, both are higher singnitficant difference ( t=4.4052, P＜0.0001 ), but mirror regions were not singnificant difference before and after ILIB (t=1.6995, P＞0.05). BFCR% quantitative results of locus were higher mirror regions, and higher singnificant difference (t=4.5278 p＜0.0001 )。 Conclusion: ILIB can improve the rCBF and cerebral function of patients with brain infarction, and provoke function of brain cells. Some new evidence was provided for ILIB treatment of cerebral ischemia     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

脑梗死患者颅内大动脉支架置入术前后vWF水平变化与血管狭窄程度的关系研究

Objective To understand the correlation between plasma von Wilebrand factor (vWF) changes after stenting and the degree of preoperative intracranial major artery stenosis in patients with acute atherosclerotie cerebral infarction. Methods This study involved 38 consecutive patients with acute cerebral infarction due to intracranial major artery atherosclerosis, who were admitted between February and October 2008 and underwent stent placement in the stenotic arteries. Thirty healthy volunteers were also recruited to serve as the control group. The patients were divided into severe stenosis group (with stenosis of the intracranial major artery≥70%) and non-severe stenosis groups. Venous blood samples were obtained from the subjects on the morning of the first and 7th days after admission to measure the plasma levels of vWF using sandwich enzyme-linked immunosorbent assay. Results The plasma levels of vWF were significantly higher in patients with acute cerebral infarction than in the control group(P=0.000). Compared with those with non-severe stenosis, the patients with severe stenosis exhibited significantly higher plasma levels of vWF (P=0.015) and greater vWF variation after stent placement (P=0.000). Conclusions In patients with acute atherosclerotic cerebral infarction due to severe intracranial major artery stenosis, the plasma levels of vWF and its postoperative variation are positively correlated to the degree of senosis of the culprit arteries, and severer stenosis is associated with greater postoperative damage of the vascular endothelium.     

Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype

Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype–phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (p < 0.003) while. DRB1*03/*04 heterozygotes were under-represented (p < 0.008). The mean age-at-onset (AAO) was 6.5 years earlier in DRB1*03/*01 heterozygotes who also had more severe quadriceps muscle weakness than the rest of the cohort. The findings indicate that interactions between the HLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM.     

Association of HLA‐DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort

Background and objective: The HLA‐DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA‐DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS. Methods: The HLA‐DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA‐DRB1 allelic frequencies were compared between OCB‐positive and OCB‐negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA‐DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB. Results: We found 206 OCB‐positive and 62 OCB‐negative patients. The HLA‐DRB1*15 allele in OCB‐positive patients had a higher frequency when compared with OCB‐negative patients (39.3% in OCB‐positive vs. 16.1% in OCB‐negative, OR = 1.38 95% CI = 1.18–1.61, P < 0.001). The other alleles did not show differences. When we compared with controls, the HLA‐DRB1*15 allele was associated with the disease only in the OCB‐positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB. Conclusions: HLA‐DRB1*15 allele is associated with OCB‐positive patients with MS when studying a Spanish MS population.     

Human leukocyte antigen alleles in patients with bipolar disorder in the Korean population

We performed an association study between human leukocyte antigen (HLA) alleles and bipolar disorder to evaluate the potentiality of HLA as a genetic marker in bipolar disorder. HLA class I and class II allele frequencies were assessed in 87 bipolar patients and were compared with those of 206 normal controls in the Korean population. HLA class I typing was performed using the microlymphocytotoxicity method, whereas class II (DRB1 and DQB1) genotyping was performed with polymerase chain reaction-sequence specific oligonucleotide probes. When the allele frequency of HLA in bipolar patients was compared with that in normal controls, there were some significant differences. Bipolar patients showed statistically significant increased allele frequencies of HLA-A29 and B54. Allele frequencies of HLA-B51 and DRB1*02 were significantly higher in normal controls. However, these results were no longer significant after correcting for the number of alleles. The results of the present study suggest that HLA alleles may not confer susceptibility to bipolar disorder in the Korean population. To clarify the genetic influence of HLA on bipolar disorder, we should conduct a consecutive study with a larger cohort of subjects.     

HLA‐DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population

Background and objective: The association of HLA‐DRB1*15 with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical phenotype is still controversial. The objectives of this study are to investigate the influence of the HLA‐DRB1 alleles on the genetic susceptibility to MS and to study their impact on disability progression in a Spanish population. Methods: HLA‐DRB1 typing was performed by PCR‐SSP in 380 patients with sporadic MS and 1088 unrelated healthy controls. Allelic frequencies were compared between groups. We studied the correlation between the different alleles and the progression of MS. Results: The HLA‐DRB1*15 allele in patients with MS had a statistically significant higher frequency when compared with controls (18.9% in patients vs. 10.1% in controls, Odds ratio (OR) = 2.07, 95% CI = 1.64–2.60, P < 0.001). In the univariate analysis, the DRB1*01 and DRB1*04 alleles were associated with a worse prognosis when considering the time to reach an EDSS of 6, whereas the DRB1*03 was correlated with a better outcome. In the multivariate analysis, the alleles*01 and *04 were demonstrated to be independent factors to have a worse prognosis. Conclusions: HLA‐DRB1*15 is associated with MS when comparing patients with unrelated healthy controls in a Spanish population. The HLA‐DRB1*01 and HLA‐DRB1*04 alleles are related to a worse prognosis when considering the time taken to reach severe disability.     

Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel

A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.     

Ethnicity-dependent association of HLA DRB1-DQA1-DQB1 alleles in Brazilian multiple sclerosis patients

OBJECTIVE: The present study focused on human leukocyte antigen (HLA) DQB1, DQA1 and DRB1 allelic variation according to ethnicity and analyzed whether susceptibility to multiple sclerosis (MS) depends on population characteristics. METHODS: Eighty-eight healthy African-Brazilians and 92 healthy white Brazilians living in Rio de Janeiro City were selected and the HLA phenotype between the two ethnic groups was compared with 44 MS patients of African descent and 40 patients of European descent. HLA class II genes were performed using polymerase chain reaction (PCR) and PCR-sequence-specific primer amplification. RESULTS: DQA1*0201-0301 alleles were associated with the white Brazilian population (P < 0.001). The DRB*1501 allele was present in White Brazilians (P=0.003), and DRB1*03-1503 in African-Brazilians. The DRB1*1501 allele confers an ethnicity-dependent MS susceptibility in White patients and the DQB1*0602 allele confers genetic susceptibility regardless of ethnicity. CONCLUSION: Heterogeneous phenotypes occur in both Brazilian ethnic groups. Taking into account that the response to immunomodulator drugs for MS treatment changes according to the DRB1*1501 allele and African-American MS patients presented poor response to the interferons, phenotype heterogeneity of HLA loci found in this study could influence therapeutic decisions in the Brazilian MS population.     

Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study

In the present study the relation between human leukocyte antigen (HLA), optic neuritis (ON) and multiple sclerosis (MS) has been investigated in 56 Iranian patients (46 females and 10 males). HLA-A and -B typing by microlymphocytotoxicity method and HLA-DRB, DQA and DQB by polymerase chain reaction based on sequence specific primers method was performed for the selected patients with ON. The diagnosis of clinically defined MS (CDMS) was confirmed in 15 of them (26.7%) during their follow-up. HLA-A24 was significantly higher in ON patients, whilst A23, A26, and A30 showed a significant decrease in these patients. HLA-A10 and A26 were absent in CDMS patients and A2 and A11 were significantly decreased in ON and CDMS patients. HLA-B5, B51, B38, B27, and B35 were significantly increased in ON patients compared with control subjects. HLA-B44, B16 and B38 alleles were not present in CDMS patients. Regarding DR locus, the frequency of HLA-DRB1*15 and DRB1*04 has been increased in CDMS patients, whilst the frequency of HLA-DRB1*07 and *11 was much higher in ON patients. In DQA region, the most frequent allele in the MS patients was DQA1*0102, which was significantly higher than ON patients, and control group. The frequency of DQA1*0103 was significantly increased in both patients group. In DQB1, the frequency of DQB1*0602 increased significantly in the MS patients. In conclusion existence of common genetic basis for early manifestations of MS could be suggested.     

河南省骨髓库汉族捐献者HLA-A、B、DR高分辨基因多态性调查分析

背景：2009年开始,中华骨髓库加大HLA高分检测的力度,可缩短配型检索周期,提高配型成功率。 目的：统计分析河南省骨髓捐献者HLA-A、B、DRB1高分辨基因多态性。 方法：河南省汉族造血干细胞志愿捐献者血样3 874人份,志愿捐献静脉血,EDTA抗凝。采用SSO HD 荧光微珠流式高分辨HLA-A、B、DRB1基因分型检测方法,对3 874份骨髓捐献志愿者血样进行高分辨分型检测,用PCR-SSP高分辨检测、SBT检测解决存在的模棱两可问题。等位基因计数法计算等位基因的基因频率。 结果与结论：共检出A 34个,B 84个,DRB1 50个,A位点基因频率处于前5位的有A*0201(0.160 9)、 A*1101(0.162 7)、 A*2402(0.160 2)、A*3001(0.080 8)、 A*3303(0.078 9);B位点处于前5位的是B*1302(0.077 7)、B*4001(0.072 2)、B*5101(0.062 8)、B*4601(0.061 2)和B*0702(0.050 7);DRB1位点处于前5位的是DRB1*1501(0.146 9)、DRB1*0901(0.131 8)、DRB1*0701(0.121 1)、DRB1*1202(0.061 2)、DRB1*0405(0.058 2)。     

HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews.

OBJECTIVE: To look for HLA class II alleles and haplotypes conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel. DESIGN: Population-based cohort of clinically definite patients with MS tested prospectively over 7 years. SETTING: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel. PATIENTS: A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls. MAIN OUTCOME MEASURES: The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease. RESULTS: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P<.001 and P =.04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*030 with MS was detected (P = .03). The MS susceptibility alleles, DRB 1* 1501, DQA1*0102, and DQB1*0602 , were found in association with the Ashkenazi patients (P<.001, P=.02, and P=.01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1* 1501, DRB1*03011, and DQB1*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P = .05, P = .05, and P = .03, respectively). CONCLUSIONS: This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients with MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.