Haptoglobin2-2 phenotype is an additional risk factor of retinopathy in type 2 diabetes mellitus.

AIMS: The aim of this study was to investigate the association between haptoglobin (Hp) phenotypes and risk of the development of diabetic retinopathy (DR) in patients of type 2 diabetes mellitus. MATERIALS AND METHODS: This cross-sectional study included 45 normotensive type 2 diabetic patients (duration more than 5 years) admitted in the hospital divided into two groups (with and without DR) on the basis of fundus examination by direct ophthalmoscopy. Serum samples of all patients were subjected for Hp phenotyping by polyacrylamide gel electrophoresis. RESULTS: DR was associated significantly in diabetic patients with Hp2-2 phenotype (79.31%) than diabetic patients with Hp2-1 phenotype (43.75%) and Hp2-2 had higher odds ratio (OR) for DR in univariate analysis (OR 4.929, [95% confidence interval [CI] (1.297-18.733)], P = 0.016) and multivariate analysis (OR 7.704 [95% CI (0.887-66.945)], P = 0.064). Furthermore, Hp2-2 was associated significantly with severe forms of DR. CONCLUSION: Hp2-2 phenotype is associated with susceptibility to DR showing a graded risk relationship to the number of Hp2 alleles. Determination of Hp phenotype may be useful in the risk assessment and management of DR.

B-cell-activating factor is a regulator of adipokines and a possible mediator between adipocytes and macrophages

3T3-L1 adipocytes express the B-cell-activating factor (BAFF) and three different BAFF receptors (BAFF-Rs). Furthermore, BAFF expression is regulated by inflammatory modulators, such as tumor necrosis factor-alpha and rosiglitazone. Here we investigated the function of BAFF in 3T3-L1 adipocytes and RAW 264.7 macrophages. We examined adipokine expression in 3T3-L1 adipocytes treated with 10 ng ml-1 BAFF. We also examined inflammatory molecule expression in RAW 264.7 macrophages treated with 10 or 100 ng ml-1 BAFF. We examined BAFF expression in the coculture of 3T3-L1 adipocytes and RAW 264.7 macrophages, as well as in white adipose tissue (WAT) of diet-induced obese (DIO) mice. We found that BAFF decreases leptin and adiponectin expression, but increases the expression of proinflammatory adipokines monocyte chemotactic protein-1, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and haptoglobin. Coculturing the two cell types resulted in increased BAFF mRNA and protein expression, as well as modulation of BAFF-R mRNA expression in both cell types. These data indicate that BAFF might mediate adipocyte and macrophage interaction. When RAW 264.7 macrophages were treated with BAFF, BAFF-R expression was modulated as in coculture, and nitric oxide synthase and IL-6 expression increased. BAFF expression also increased in WAT of DIO mice. We propose that BAFF can regulate adipokine expression and possibly mediate adipocyte and macrophage interaction.

Anaphylactic Transfusion Reaction in a Patient with Anhaptoglobinemia: The First Case in Korea

Anaphylactic transfusion reactions are rare complications of blood transfusions. Anhaptoglobinemia, a condition that has high incidence in Asia, can cause allergic transfusion reactions or anaphylaxis in severe cases. A 50-yr-old Korean woman was diagnosed with relapsed acute promyelocytic leukemia. She developed thrombocytopenia during chemotherapy and an anaphylactic transfusion reaction on the 4th and 5th platelet transfusions immediately after the transfusion of the platelet concentrates was initiated. Blood analysis showed no detectable serum haptoglobin. We examined her genetic phenotype and detected anhaptoglobinemia, which occurs because of an allelic deletion in the Hp gene cluster. The presence of an antibody against haptoglobin was detected by performing ELISA. To prevent anaphylactic reactions, apheresis platelets were transfused after washing. Consequently, anaphylactic transfusion reactions did not develop. Here, we report the first case of anhaptoglobinemia causing anaphylactic transfusion reaction in Korea.

Genótipos de haptoglobina e hipertensão refratária em pacientes com diabete melito tipo 2 / Haptoglobin genotypes and refractory hypertension in type 2 diabetes mellitus patients

FUNDAMENTO: Tem sido sugerido que o polimorfismo da haptoglobina pode influenciar na patogênese das complicações microvasculares e macrovasculares em pacientes diabéticos. OBJETIVO: O objetivo principal deste estudo transversal foi de realizar uma investigação da existência ou não de uma associação entre os genótipos de haptoglobina e a prevalência de eventos isquêmicos cardiovasculares (angina estável, angina instável e infarto agudo do miocárdio), hipertensão arterial sistêmica, hipertensão refratária, obesidade e dislipidemia em 120 pacientes com diabete melito tipo 2, seguidos no Hospital Universitário da Unicamp, em Campinas, Estado de São Paulo. MÉTODOS: A genotipagem da haptoglobina foi realizada por reações em cadeia da polimerase alelo-específicas. As frequências dos genótipos de haptoglobina foram comparadas com a presença/ausência de doença cardiovascular, hipertensão arterial sistêmica, hipertensão refratária, obesidade e dislipidemia; medições de pressão arterial sistólica e diastólica; glicemia, colesterol (total, lipoproteínas de alta densidade - HDL e lipoproteínas de baixa densidade - LDL) e triglicerídeos; assim como níveis de creatinina sérica. RESULTADOS: Embora nenhuma associação entre o genótipo de haptoglobina e a presença de doença cardiovascular tenha sido identificada, encontramos um excesso significativo de pacientes com o genótipo Hp2-1 entre as pessoas com hipertensão refratária, que também apresentavam uma maior pressão arterial sistólica e diastólica e níveis de colesterol total e LDL. CONCLUSÃO: Nossos resultados sugerem que os pacientes com diabete melito tipo 2 com o genótipo Hp2-1 podem apresentar uma maior chance de desenvolver hipertensão refratária. Estudos adicionais em populações diabéticas são necessários para confirmar esses achados.

BACKGROUND: It has been suggested that haptoglobin polymorphism may influence the pathogenesis of microvascular and macrovascular complications in diabetic patients. OBJECTIVE: This cross sectional study was carried out to investigate the existence or not of an association between haptoglobin genotypes and prevalence of ischemic cardiovascular events (stable angina, unstable angina and acute myocardial infarction), systemic arterial hypertension, refractory hypertension, obesity and dyslipidemia in 120 type-2 diabetes mellitus patients followed up at Hospital de Clínicas da UNICAMP in Campinas, São Paulo state, southeastern Brazil. METHODS: Haptoglobin genotyping was performed by allele-specific polymerase chain reactions. The frequencies of the haptoglobin genotypes were compared with the presence/absence of cardiovascular disease, systemic arterial hypertension, refractory hypertension, obesity and dyslipidemia; systolic and diastolic blood pressure measurements; plasma levels of glucose, cholesterol (total, high density lipoprotein-HDL and low density lipoprotein-LDL) and triglycerides; and serum creatinine levels. RESULTS: Although no association between haptoglobin genotype and the presence of cardiovascular disease could be identified, we found a significant excess of patients with Hp2-1 genotype among those with refractory hypertension, who also had higher systolic and diastolic blood pressure, and total and LDL cholesterol levels. CONCLUSION: Our results suggest that type-2 diabetes mellitus patients with the Hp2-1 genotype may have higher chances of developing refractory hypertension. Further studies in other diabetic populations are required to confirm these findings.

Haptoglobin polymorphism among the tribal groups of southern Gujarat.

BACKGROUND: Gujarat is located at the western most point of the Indian subcontinent. Valsad and Surat districts are part of the ‘tribal belt’of Gujarat and constitute 29.1% of total tribal population of Gujarat. These tribal populations are a rich source of gaining insights in the patterns of genetic diversity and genetico-environmental disorders against the back drop of their ecological, historical and ethnographic aspects. AIM: The objectives were to find out a) the genetic diversity among the tribes of Gujarat with reference to haptoglobin (Hp) locus b) the relationship between Hp polymorphism and sickle cell anemia/trait. MATERIALS AND METHODS: 431 individuals belonging to eight tribal groups were studied for Hp polymorphism using polyacrylamide disc gel electrophoresis (PAGE). Hb*S was screened by dithionate tube turbididy (DTT) test and confirmed using cellulose acetate membrane electrophoresis (CAME). STATISTICAL ANALYSIS: Allele frequency was calculated by direct gene counting method. Average heterozygosity and gene diversity were computed using software DISPAN. Analysis of molecular variance (AMOVA) was estimated using software ARLEQUIN version 3.1. RESULTS AND CONCLUSIONS: Pattern of allele frequency distribution showed preponderance of Hp2 allele in all the eight tribal groups, which is in accordance with its frequency in different populations of Indian subcontinent. Total average heterozygosity (HT) was found to be low (0.160) but the level of genetic differentiation (GST) was found to be moderately high (5.6%). AMOVA analysis indicated least among group variance between west and south Indian populations (-0.04%) indicating the affinities of the tribes of Gujarat with that of Dravidian speaking groups. Analysis of Hp phenotypes among sickle cell anemia/ trait individuals revealed a high frequency of Hp 0-0 phenotype (92.7%) among SS individuals as opposed to only 9.7% among AS individuals, reaffirming the selective advantage of HbAS state in relation to hemolytic disorders.

Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities

Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp*1 and Hp*2 alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp*1 allele has two subtypes, Hp*1F and Hp*1S, that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56), Kalunga Afro-descendants (n = 70) and an urban population (n = 132) were determined by allele-specific PCR. The Hp*1F allele frequency was highest in Kalunga (29.3 percent) and lowest in Kayabi (2.6 percent). The Hp*1F/Hp*1S allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp*1F allele. However, despite the large variation in Hp*1F frequencies, results of FST (0.0291) indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp *1F and Hp*1S frequencies among non-Amerindian Brazilians.

Polymorphism of Haptoglobin in Patients with Premature Rupture of Membrane

PURPOSE: To investigate whether allelic polymorphism of haptoglobin (Hp) is associated with premature rupture of membrane (PROM), the Hp phenotypes of pregnant women with PROM were analyzed. PATIENTS AND METHODS: The Hp phenotypes of 221 pregnant Korean women (187 control and 34 PROM patients) were determined by benzidine/hydrogen peroxide staining, following native polyacrylamide gel electrophoresis of hemoglobin-mixed sera. The Hp allele frequencies were calculated from the data of Hp phenotypes, and overall association with PROM was evaluated using Pearson Chi-Square test. RESULTS: The polymorphic distribution of the patients cohort who underwent a normal delivery (control group) was similar to that of healthy Koreans. In contrast, however, patients with PROM showed significantly higher occurrence of the Hp 1-1 phenotype than control group (23.5% vs 8.0%). Hp 2-2 phenotype was lower in PROM cohort (38.2%) than in the control group (48.7%). The Hp1 allele frequency in PROM group was significantly higher than that in the control group (0.426 vs 0.297, p = 0.034) with odds ratio of 1.762 (95% CI: 1.038 - 2.991). CONCLUSION: These findings suggest that pregnant Korean women who possess Hp1 allele (expressed as Hp 1-1 phenotype) have higher incidence of PROM than women with Hp2 allele (expressed as Hp 2-2 phenotype). This is the first study that evaluated the significance of Hp polymorphism with respect to the development of PROM.

Association of genetic markers with coronary heart disease (myocardial infarction)--a case-control study.

A case-control study was carried out on patients of myocardial infarction selected from coronary care unit of Lok Nayak Jai Prakash Narayan Hospital, Delhi. The study was carried out to determine the association of haptoglobin (Hp), transferrin (Tf) and complement component 3 (C3) polymorphism with myocardial infarction. The frequency of allele Hp1 was found to be 0.159 in cases studied and 0.058 in controls. The frequency of gene TfC was found to be 0.987 in cases of study and 0.992 in controls. Similarly, frequency of CS3 gene was found to be 0.985 and 0.990 in cases studied and controls respectively. The comparison between cases studied and controls with respect to TfC and CS3 polymorphism was found to be statistically non-significant while the comparison between cases studied and controls for Hp polymorphism was found to be statistically significant (chi 2 = 21.88, p < 0.01).

Interaction between ABO and haptoglobin systems in a Chilean population of mixed ancestry

Para investigar a associaçäo entre os grupos sangüíneos ABO e a haptoglobina sérica (Hp), nós tipamos Hp e os grupos ABO em 288 crianças, que foram selecionadas ao acaso dentre aquelas que começaram o primeiro grau escolar em 1973 na área metropolitana de Santiago, Chile. Esta regiäo tem um componente ameríndio de 40 por cento e um componente caucasiano (principalmente espanhóis) de 60 por cento. Nossos resultados contrastam com estudos prévios que relataram que Hp*1 variou entre os grupos ABO da seguinte maneira: O

Composición genética de la población chilena: los yamanas de Ukika / Genetic composition of chilean population: the yamanas from Ukika

The genetic composition of a group of 24 Yamana indians that survive in Puerto Williams, navarino Island, Chile (parallel 55 south of Tierra del Fuego), was studied. Results showed that these indians have a different genetic composition than Pehuenche indians, specially for HLA system and sterase D. This fact validates the hypothesis based on archeological and antropological evidence, about the paleoindian origin of Yamanas

Serum protein polymorphisms and malaria in Madya Pradesh, India.

The relationship of serum protein polymorphisms to the presence of malaria antibodies was studied in 473 muria gond tribal subjects from Bastar district, Central India, an area endemic for both P. falciparum and P. vivax infection. A control group of 100 subjects in Delhi, which has a low prevalence of malaria, was also studied. Serum proteins (transferrin, haptoglobin and albumin) were analyzed for polymorphic variants by starch gel electrophoresis. Malarial antibodies were assayed by enzyme linked immunosorbent assay (ELISA), while thin blood films were screened for the presence of malaria parasites. Among serum proteins transferrin CD variant showed significant correlation with malarial infection. There were no significant differences observed between Hp1 and Hp2 variants of haptoglobin in relation to presence of malarial antibodies. Statistical analysis for albumin variants was not attempted because the number of individuals showing abnormal bands was small.

Estudio del origen monocigotico de trillizos del mismo sexo, por comparación de sus grupos sanguineos, de haptoglobinas y los dermatoglifos

Con el propósito de establecer si eran trillizos de origen monocigótico se analizaron los grupos sanguíneos, las haptoglobinas y los dermatoglifos en tres grupos de individuos de un mismo sexo, los cuales presentaban muchas características fenotípicas iguales. Los resultados de los grupos sanguíneos en los tres grupos estudiados revelaron que no existía diferencia en relación con los veinte grupos sanguíneos analizados. Los resultados de la electroforesis de las haptoglobinas demostró que cada grupo de trillizos era del tipo Hp2-1 heterocigotos. El estudio del patrón digital de las manos y de los pies de cada individuo en cada grupo demostró ser muy similar; al igual que el conteo total de arrugas