C3 polymorphism in a Danish cystic fibrosis population and its possible association with antibody response

The C3 types of human serum are reported for a material of 113 Danish cystic fibrosis patients, age 0-30 years. The frequency of the C3F gene was 0.2832 which was significantly higher (p less than 0.0005) than the frequency found in a control group of 224 healthy babies (C3F = 0.1585). It also differed significantly (p less than 0.01) from the C3F gene frequency of 0.1780 found in 177 blood donors, age 20-24 years. A significant association between any of the C3 phenotypes and the most serious infection in cystic fibrosis, chronic mucoid P. aeruginosa infection, or the antibody response against these bacteria was not found.     

Complement C6 and C7 polymorphisms in Japanese patients with chronic glomerulonephritis

C6 and C7 types were studied in 158 Japanese patients with different types of chronic glomerulonephritis: 75 patients with IgA nephropathy (IgA-N); 49 patients with idiopathic membranous nephropathy (IMN), and 34 patients with minimal-change nephrotic syndrome (MCNS). There were significant differences in the C6 and C7 allele and phenotype frequencies between the patient groups and controls. A strong association was found between IgA-N and C7 5 phenotype (p less than 0.001, RR = 12.71), and between MCNS and C7 5 phenotype (p less than 0.001, RR = 14.20). A significant association between MCNS and C6 B2 phenotype (p less than 0.05, RR = 2.42) was also found. In the IMN patient group, a significant association with C7 4 phenotype (p less than 0.05, RR = 2.42) was observed. Thus, C6 and C7 phenotypes may be causative factors in the development of chronic glomerulonephritis.     

ABO blood groups, intestinal alkaline phosphatase and haptoglobin types in patients with serum hepatitis

A series of 150 patients with serum hepatitis were examined for the incidence of the Australia antigen (HBsAg) and associations with ABO blood groups, haptoglobin types and occurrence of intestinal serum alkaline phosphatase. Among the patients studied 11.3% were positive for HBsAg. When compared to controls patients with blood group O showed a significantly increased risk for serum hepatitis (p less than 0.05), while those with group B showed a decreased risk (p less than 0.01). The presence of the intestinal fraction of alkaline phosphatase showed a negative association with serum hepatitis (p less than 0.01) and there was no significant association between alkaline phosphatase types and ABO groups among the patients. The frequency of the Hp1 gene was significantly increased (p less than 0.01) among the patients as compared to controls.     

Serum protein groups (Hp, GC, C3) in patients with gastric carcinoma.

The phenotypes and gene frequencies of 3 serum protein systems (Hp, GC and C3) were studied in 114 consecutive patients from all over Greece with gastric carcinoma. Healthy Greeks studied previously in our Department served as controls. No significant differences were found between patients and controls concerning Hp. Significant differences were found in the GC and C3 systems; GC 2-1 and C3F phenotype as well as C3*F gene frequencies were significantly higher in patients than in controls.     

Studies of HLA, factor B (Bf), complement C2 and C4 haplotypes in type 1 diabetic and control families from northern Sweden

The HLA-A,-B,-C,-DR antigens and the complement factors C2, C4 and Bf were determined in 30 insulin-dependent diabetes mellitus (IDDM) patients and 30 healthy controls from northern Sweden. Family studies allowed the deduction of extended haplotypes in the HLA and complement systems. Phenotype studies revealed significant associations between IDDM and HLA-DR4 (p less than 0.001), HLA-DR3 (p less than 0.05), HLA-DR3/4 (p less than 0.025), C4-B3 (p less than 0.001) and Bf-S (p less than 0.025). Haplotype studies showed that the extended haplotype [HLA-B15, C2-1, C4-A3B3, Bf-S, HLA-DR4] had a particularly strong association to IDDM. This haplotype was found in 10 out of 30 IDDM probands but in none of 30 control children and accounts for practically all the C4-B3 allotypes among the 30 IDDM probands. The C4-B3 gene therefore seems to be a valuable marker for IDDM. No haplotype containing HLA-DR3 was increased in frequency among the IDDM probands. The extended haplotype [HLA-B7, C2-1, C4-A3B1, Bf-S, HLA-DR2] present among the controls was absent in the IDDM probands. The frequency of the extended haplotype [HLA-B15, C2-1, C4-A3B3, Bf-S, HLA-DR4] was increased also among the parents to the IDDM probands compared to those of the control parents, whereas the frequency of [HLA-B7, C2-1, C4-A3B1, Bf-S, HLA-DR2] was decreased. The extended haplotype [HLA-B8, C2-1, C4-B1, Bf-S, HLA-DR3] was more common among the males (p less than 0.05) compared to the females in the total material. The family analysis showed that 3 out of 5 affected sibs shared both haplotypes with their IDDM proband. This was the case for only 3 out of 35 unaffected sibs.     

Bf and C3 complement types in rheumatoid arthritis

Bf and C3 complement types were studied in 100 male and 100 females patients from northern Sweden with erosive rheumatoid arthritis (RA) and compared with population controls. A significantly decreased frequency of the Bf FS phenotype was found particularly in males and in patients with a family history of polyarthritis. Significant Bf associations were also found with a more severe form of RA (functional classes III and IV) and with high titers of the rheumatoid factor. No significant difference with respect to C3 phenotype and gene frequencies was found between RA patients and controls. Thus, the association between RA and C3F found in some previous investigations was not confirmed.     

GC and C3 serum groups in peptic ulcer.

The phenotypes and gene frequencies of two serum protein systems (GC, C3) were studied in 238 consecutive patients with peptic ulcer from all over Greece. 173 patients had duodenal ulcer and 65 had gastric ulcer. Healthy Greeks studied previously in our department served as controls. No significant differences were found between the studied groups and the controls as far as GC was concerned. However, significant differences emerged in C3; the C3*F gene was almost twice more common and the C3F phenotype almost three times more frequent in patients than in controls.     

Polymorphisms of serum proteins in Japanese patients with vascular diseases. I. Factor XIIIB, plasminogen and complement types in primary varicose veins.

The polymorphisms of the B subunit of coagulation factor XIII (F13B), plasminogen (PLG), complement C6, C7, factor B (BF) and factor I (IF) were studied among 21 unrelated Japanese patients with primary varicose veins (PVV) by isoelectric focusing followed by immunoblotting. The allele frequencies for F13B*2 and IF*A in PVV patients were significantly higher (F13B*2, p = 0.0047; IF*A, p = 0.0006) than those in healthy controls (n = 60). Significant associations of F13B 2 allotype [p = 0.0220, relative risk (RR) = 13.9] and IF A allotype (p = 0.0006, RR = 10.0) with PVV were observed; however, no significant association of PLG, C6, C7 or BF allotype with the disease was found.     

Complement factor C4 in schizophrenia

The complement factor C4 was studied in 165 schizophrenic patients and in 330 controls. A highly significant increase in the frequency of C4B deficiency (BQO) was found among the schizophrenic patients compared with controls (p less than 0.0005).     

Complement phenotypes in patients with psoriasis

Phenotype frequencies for the complement proteins C4A, C4B, Bf (factor B) and C3 were performed for 49 Caucasian patients with psoriasis. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of healthy regional Caucasian controls, p less than 0.001, relative risk = 6.28. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and to produce a non-functional gene product when it occurs with the B17 allele. HLA B17 is known to be associated with psoriasis in many Caucasian populations. Additional findings in the present study were a significant reduction in the C4B*2 allele frequency, a non-significant increase in the Bf*F allele frequency and no difference for Bf or C3 phenotype frequencies in the patients with psoriasis as compared to the controls.     

Associations between the two serum proteins haptoglobin and transferrin and leukaemia

Haptoglobin and transferrin (TF) types were determined for 134 patients with leukaemia of the four most common types: acute lymphocytic (ALL), chronic lymphocytic (CLL), acute myelocytic (AML) and chronic myelocytic leukaemia (CML). The phenotype HP1 was found to have an increased incidence in the total patient group due to an increased incidence in those with AML, ALL and CML compared with controls, but not in those with CLL. Although tests of association applied to each of the samples of the four common types of leukaemia produced no significant chi 2 values, they did indicate that the relative incidence (RI) was just under 2 for the groupings of the acute forms ALL and AML, the myelocytic forms AML and CML and for the combination of ALL, AML and CML, respectively. All these associations were statistically significant (p less than 0.05). Analysis of TF subtypes and leukaemia indicated a significantly increased frequency of TF C1C1 among leukaemia patients compared with controls (p less than 0.005). Analysis of the samples of each of the four common types suggested that while the RI was raised in all but ALL patients, the association was significant only in AML patients (p less than 0.05). However, when the two myelocytic types were combined the RI was 2.3 and the association was highly significant (p less than 0.005). No such association could be detected in the lymphocytic forms.     

Disturbances of insulin in British Asian and white men surviving myocardial infarction.

OBJECTIVE--To examine the role of insulin as a cardiovascular risk factor in British Asian and white men. DESIGN--Case-controlled study of survivors of first myocardial infarction. SETTING--District general hospital. PATIENTS--Consecutive series of 76 white and 74 Asian men who survived first myocardial infarction compared with 58 white and 61 Asian male controls without coronary artery disease who were randomly sampled from the community. RESULTS--More Asians than white subjects had impaired glucose tolerance or overt diabetes as measured by the two hour glucose tolerance test (23/74 (32%) v 11/76 (15%) (p less than 0.001) among patients; 17/61 (28%) v 3/58 (6%) (p less than 0.001) among controls). Insulin and C peptide concentrations were higher in both patient groups than in respective controls (p less than 0.001) and higher in Asian than in white subjects, irrespective of their glucose tolerance. Triglyceride concentrations were higher in patients than in controls (1.92 (SD 1.05) v 1.43 (0.82) mmol/l among Asian men; 1.65 (0.83) v 1.3 (0.61) mmol/l among white subjects; p less than 0.001). Total cholesterol concentrations were lower in both groups of Asians than in respective white subjects (5.78 (0.99) v 6.22 (1.04) mmol/l (p less than 0.01) among patients; 5.54 (1.01) v 5.65 (1.11) mmol/l (p less than 0.6) among controls). High density lipoprotein cholesterol concentrations were lower in Asian than in white subjects. The ratio of total cholesterol to high density lipoprotein cholesterol was significantly higher (p less than 0.001) in both patient groups (6.69 (1.81) in Asian patients and 6.31 (1.91) in white patients) than in respective controls (5.24 (1.19) and 4.77 (1.43)). Regression analysis identified C peptide concentration and the ratio of total to high density lipoprotein cholesterol as powerful independent predictors of myocardial infarction in Asian and white men. Total cholesterol concentration predicted infarction in white but not in Asian men. CONCLUSIONS--Secretion and hepatic extraction of insulin are high in survivors of myocardial infarction and especially high in British Asians. Tissue resistance to the action of insulin, giving rise to increased pancreatic secretion, may be an important risk factor for coronary artery disease in both ethnic groups and may be partly responsible for the high incidence of diabetes and coronary artery disease in Asian populations.     

Transferrin C subtypes and occupational photodermatosis of the face

In a factory in northern Sweden where 120 workers were uniformly exposed to photoactive substances 73 developed occupational facial eczema while 47 showed no reaction. The workers were examined with respect to 16 genetic marker systems: HLA, blood groups (ABO, Rh, MNSs, P, K, Le and Fy) and serum groups (Hp, Tf, Gc, Pi, Bf, C3, C4 and C6). Between reactors and nonreactors the following differences were found: (1) a significant decrease (p less than 0.05) of HLA A11 among the reactors; (2) a significant increase (p less than 0.05) of the C3 FS type among the reactors; (3) a highly significant increase (p less than 0.001) of the transferrin C2 gene and of the C2 variant among the reactors. The association with Tf C2 remained significant also after correction for number of significance tests. Since transferrin (iron) is known to catalyze the formation of hydroxyl radicals we hypothesize that the Tf C2 variant is more efficient in promoting radical formation and thereby cell damage. Other results supporting the notion that transferrin C2 may be associated with an increased susceptibility to toxic damage are discussed.     

Human leucocyte antigens A,B, C,and DRW in idiopathic "warm" autoimmune haemolytic anaemia.

Twenty patients with idiopathic "warm" autoimmune haemolytic anaemia and 40 controls were types concurrently for human leucocyte antigens (HLA) A, B, C, and DRW. There was a significantly stronger association of HLA-B8 with the disease (chi 2 = 10.39; p = 0.018) than HLA-DRW3 (chi 2 = 3.71; P = 0.35) and the patients also showed a significant increase in BW6 homozygosity (chi 2 = 7.13; P = 0.01) and a corresponding reduction in BW4 (chi 2 = 7.13; P = 0.02). (All p values corrected for number of antigens at each locus.) These findings suggest that susceptibility to idiopathic autoimmune haemolytic anaemia is associated more closely with the HLA-B locus than with DRW3.     

Haptoglobin and transferrin types in schizophrenia

Haptoglobin and transferrin types were studied in schizophrenic patients and controls. In the haptoglobin system a significant departure from the Hardy-Weinberg equilibrium with an excess of heterozygotes was found among the patients (p less than 0.01). The distribution of haptoglobin types in the schizophrenic patients was significantly different from that in the controls. The distribution of transferrin types showed a good agreement with the Hardy-Weinberg equilibrium. There was no significant difference between patients and controls with respect to transferrin types.     

Haptoglobin groups and lung cancer

Haptoglobin groups were investigated in 309 patients with primary lung cancer divided by sex, smoking habits and tumor type. Patients with squamous epithelial cancer and oat-cell cancer showed no significant difference from normal controls. Among patients with pulmonary adenocarcinoma the frequency of the Hp 2-2 type was significantly (p less than 0.05) lower compared to the controls, with a corresponding increase of the Hp 1-1 and Hp 2-1 types. This difference was more pronounced (p less than 0.025) among females with pulmonary adenocarcinoma.     

Frequent joining of Bcl-2 to a JH6 gene in hepatitis C virus-associated t(14;18)

The t(14;18) chromosomal translocation, which joins the Bcl-2 proto-oncogene to an Ig J(H) gene, has increased prevalence in patients chronically infected with hepatitis C virus (HCV). We now establish a link between the molecular structure and clinical occurrence of HCV-associated t(14;18). A t(14;18) was detected by PCR in leukocytes from 22 of 46 HCV-infected patients (48%) and 11 of 54 healthy controls (20%) (p = 0.0053). Nucleotide sequence analysis of the Bcl-2/J(H) joins found a J(H)6 gene in 18 of 22 (82%) t(14;18) from HCV(+) patients, and 3 of 8 (38%) from controls (p = 0.031). The t(14;18) rarely contained J(H) gene mutations, or an intervening region sequence suggestive of D gene rearrangement or templated nucleotide insertion. Analysis of published t(14;18) nucleotide sequences established that the J(H)6 prevalence in t(14;18) from normal/nonneoplastic controls (48%) was significantly lower than in t(14;18) from our HCV(+) patients (p = 0.004) or from non-Hodgkin's lymphomas (66%, p = 0.003). We conclude that the increased prevalence of t(14;18) in HCV(+) patients occurs with a strong bias for Bcl-2/J(H)6 joins. In this regard, HCV-associated t(14;18) more closely resemble t(14;18) in lymphomas than t(14;18) from normal subjects.     

502例丙型肝炎患者病毒基因分型及与性别和年龄的关系研究

目的:探讨502例丙型肝炎患者病毒基因分型的情况,分析其与性别和年龄的关系,为丙型肝炎的防治提供参考。方法:收集贵州地区502例丙型肝炎患者的血液标本,采用PCR-荧光探针法检测丙型肝炎病毒基因型,并对检测数据进行统计学分析。结果:共检出4种基因型及5种基因亚型,主要以1b型、3b型为主,其次是6a、3a型,2a型较少。不同性别丙型肝炎病毒(HCV)基因型分布比较,差异有统计学意义(x²=11.029,P=0.026),男、女性患者均以1b型、3b型为主要基因型,但男性感染者明显多于女性。各个年龄组HCV基因型分布比较,差异有统计学意义(x²=102.946,P=0.000),40-59岁组感染者最多,以1b型为主,其次是20-39岁组,以3b型为主,≥60岁组感染人数较少,以1b型为主。结论:贵州地区HCV呈现多基因型分布,1b、3b型为主要流行基因型,6a、3a型次之,其余基因型较少,不同性别、年龄的HCV基因型分布存在差异性。     

非综合征性耳聋(NSHL)患者Cx26基因突变分析及两种突变体的亚细胞定位

为分析中国人群非综合征性耳聋(Nonsyndromic hearing loss, NSHL)患者Cx26基因的突变情况和特性, 研究其中两种突变的亚细胞定位情况, 文章运用PCR直接测序的方法对139例无亲缘关系的NSHL患者进行突变筛查, 将两种突变p.F115C和p.V37I构建到pEGFP表达载体, 并转染Hela细胞, 研究其细胞表达和定位情况。在139例无亲缘关系的NSHL患者中, 31例患者检测到Cx26基因突变, 检出率为22.3%。一共检测到10种不同类型的碱基变异, 包括6种突变和4种多态, 其中包括1种未见报道的新变异p.F115C。p.F115C和p.V37I两种突变体转染Hela细胞后, 亚细胞定位情况与野生型无差异, 初步研究表明这两种突变不影响该蛋白形成细胞间隙连接通道。     

Low plasma C4 concentrations: association with microangiopathy in insulin dependent diabetes.

Plasma C4 concentrations were measured in insulin dependent diabetics with and without microangiopathy and in controls. The diabetics had significantly lower C4 values than controls (p less than 0.001), and patients with insulin dependent diabetes and microangiopathy had lower values than those without this complication (p less than 0.001). There was a 7.1-fold increase in the prevalence of complications in the diabetics with low C4 values. Of 41 diabetics whose rate of albumin excretion was measured, 13 had increased rates and 11 of these had low C4 concentrations. Low plasma C4 concentration in insulin dependent diabetes is strongly associated with microvascular disease and may identify diabetics with a particular propensity to develop this complication.