The role of the Duffy antigen-related chemokine receptor in psoriasis vulgaris

Chemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverse chemokines of both C-C and C-X-C families. It is co-localized with blood group antigens of the Duffy system on the same glycoprotein and expressed on red blood cells as well as post-capillary blood vessels. In the present study three aspects of Duffy pathophysiology were studied: firstly the amount of IL-8 and RANTES binding to red blood cells and its correlation to disease activity of psoriatic patients, secondly the distribution of Duffy phenotype among psoriatic patients and thirdly the expression of Duffy antigen in normal vs psoriatic skin. Red blood cells from psoriatic patients (n=50) were lysed by triton X (1%) and supernatants tested in IL-8- and RANTES sandwich-ELISA. Duffy phenotype of psoriatic patients (n=50) was assessed by typing red blood cells with specific antisera in indirect Coombs technique. For immunohistochemical detection in normal and psoriatic skin (n=10 respectively) a specific monoclonal antibody (Fy6) was used. Neither IL-8- nor RANTES-levels on red blood cells correlated to disease activity and distribution of Duffy phenotype in psoriatics was not significantly altered when compared to the normal population. Furthermore, Duffy antigen was expressed in a similar pattern in normal and psoriatic skin at all parts of vasculature, albeit much more abundantly in diseased skin. Altogether, chemokine binding to red blood cells seems of minor importance in psoriasis. However, Duffy antigen together with other binding mechanisms like proteoglycans may play a role at local level by binding locally produced chemokines. Thus biological effects of chemokines are both restricted and focussed to dermal tissue.     

Blood groups in Native Americans: a look beyond ABO and Rh

The study presents comparisons between blood group frequencies beyond ABO and Rh blood systems in Native American populations and previously published data from Brazilian blood donors. The frequencies of Diego (c.2561C>T, rs2285644), Kell (c.578C>T, rs8176058), Duffy (c.125A>G, rs12075, c.1−67T>C, rs2814778) and Kidd (c.838A>G, rs1058396) variants in Kaingang (n=72) and Guarani (n=234) populations from Brazil (1990-2000) were obtained and compared with data from these populations sampled during the 1960s and with individuals of different Brazilian regions. Data showed high frequencies of DI*01 and FY*01 alleles: 11.8% and 57.6% in Kaingang and 6.8% and 75.7% in Guarani groups, respectively. The main results indicated: (1) reduction in genetic distance over time of Kaingang and Guarani in relation to other Brazilian populations is suggestive of ongoing admixture; (2) significant differences in some frequencies of blood group markers (especially Diego, Kidd and Duffy) in relation to Native Americans and individuals from different geographical regions of Brazil. Our study shows that the frequency of red blood cell polymorphisms in two Native American groups is very different from that of blood donors, when we evaluated blood groups different from ABO and Rh systems, suggesting that a better ethnic characterization of blood unit receptors is necessary.     

Duffy blood group determinants and malaria in India

Two hundred and fiftyeight Muria Gond subjects from Bastar district in Central India and 97 subjects from Delhi were typed for Duffy blood group determinants, and their blood examined for malaria antibodies as well as for presence of malarial parasites. We found the Duffy-negative phenotype in high prevalence among Muria Gonds, while in Delhi no subject was observed to be Duffy-negative. Frequencies of seropositivity for malaria antibodies (the test did not distinguish betweenP. falciparum andP. vivax) were not significantly different among subgroups of Muria Gond individuals with different Duffy blood group phenotypes. Examination of thin and thick blood films did not reveal infection withP. vivax in Duffy-negative individuals. Our results suggest that Duffy-negative individuals, though resistant to infection withP. vivax, are not resistant to infection withP. falcipanun.     

Brief communication: Molecular characterization of O alleles at the ABO locus in Chilean Aymara and Huilliche Indians

A molecular characterization of alleles O1, O1variant (O1v), and the mutation G542A of the ABO blood group was performed in two Amerindian populations of Chile, the Aymara (n = 84) and the Huilliche (n = 75). In addition, a sample of 82 individuals of Santiago belonging to the mixed Chilean population was typed for comparative purposes. The polymorphisms which allow for molecular differentiation of different alleles of the O blood group were studied in genomic DNA. The mutations G188, G261-, G542A, T646A, and C771T, described for alleles O1, O1v, and G542A, were determined using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) technique. All individuals studied were group O homozygotes for the deletion G261-, which defines the O1 alleles. Results obtained indicate that allele O1v exhibits frequencies of 0.65, 0.81, and 0.60 in Aymara, Huilliche, and Santiago populations, respectively. The frequencies of allele O1(G542A) were 0.119, 0.113, and 0.079 in the same populations. Frequencies for alleles O1 and O1v obtained in the Chilean populations studied concur with the results obtained by other authors, respecting the greater frequency of allele O1v as well as with its heterogeneous distribution in aboriginal South American populations. In Chilean populations, Allele G542A exhibits lower frequencies than those described for indigenous populations from Brazil and may be used as an Amerind admixture marker.     

宁夏回族红细胞血型的研究

调查了219名宁夏回族的 ABO、MNSs、Rhesus、P、Lewis、Duffr、Kidd Diego 、Kell、Lutheran和Xg等11种系统的红细胞血型。结果表明,宁夏回族有较高的q(0.2530)、Fy~a(0.9270)、CDe(0.6225) 和E(0.2660) 等基因或染色体频率;d(0.0557)、s(0.0594)、P_1(0.1316)和 Le~a(0.3882)等基因频率较低;而未发现K和Lu~a基因;Di~a的频率为0.0349,也处于低水平;Ns(0.4984)连锁率高于 Ms(0.4422);Xg~a基因频率为0.4432。11个系统的红细胞血型的分布和遗传距离分析均反映了宁夏回族的遗传组成具有我国北方民族的特征,尤其接近于北方汉族和蒙古族,与新疆维吾尔族则存在较大的差异。     

客家人的红细胞血型分布

对父母双方上溯三代均为客家人的广东梅县200名 (其中男89人,女111人) 健康学生进行了红细胞血型ABO,MNSs,Rh,Kidd,Duffy,Diego,Xg,Lewis及P等系统的分布调查。结果显示,客家人的基因频率S=0.0250,NS=0,pl=0.0917和Fyb=0.0300,都是汉族人群中最低的。其它基因频率为r=0.6632,p=0.1863,q=0.1505;m=0.5250,n=0.4750,MS=0.0250,Ms=0.5000,Ns=0.4750,s=0.9750;C=0.6575,D=1.0000,E=0.1515,CDe=0.6226,cDE=0.1200,cDe=0.2189,CDE=0.0389;JKa=0.4642,JKb=0.4881,JK=0.0477;Fya=0.9700;Dia=0.0202,Dib=0.9798;Xga=0.3633,Xg=0.6367;P2=0.9083。发现了国内第二例Jk(a-b-)表型,未发现MNS型,NS型,NSs型,CCDEE型,CcDEE型,Fy(a-)型和Rho(-)型。Le(a+b-)型29人,Le(a+b+)型2人,Le(a-b+)型67人,Le(a-b-)型102人。客家人与国内19个群体的遗传距离计算结果表明,与客家人遗传距离最近的是福建汉族、湖南苗族、贵州汉族及广西侗族,其次为河南汉族、黑龙江汉族、陕西汉族,福建畲族及上海汉族,而与云南白族、辽宁满族、甘肃汉族、广西瑶族、广西壮族、内蒙汉族及四川彝族的遗传距离较远。与客家人遗传距离最远的是湖南土家族、海南苗族及海南黎族。     

Association of Duffy Blood Group Gene Polymorphisms with IL8 Gene in Chronic Periodontitis

The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher''s Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.     

Detection and genetic characterisation of Toxoplasma gondii circulating in free-range chickens,pigs and seropositive pregnant women in Benue state,Nigeria

Toxoplasma gondii parasites present strong but geographically varied signatures of population structure. Populations sampled from Europe and North America have commonly been defined by over-representation of a small number of clonal types, in contrast to greater diversity in South America. The occurrence and extent of genetic diversity in African T. gondii populations remains understudied, undermining assessments of risk and transmission. The present study was designed to establish the occurrence, genotype and phylogeny of T. gondii in meat samples collected from livestock produced for human consumption (free-range chickens, n = 173; pigs, n = 211), comparing with T. gondii detected in blood samples collected from seropositive pregnant women (n = 91) in Benue state, Nigeria. The presence of T. gondii DNA was determined using a published nested polymerase chain reaction, targeting the 529 bp multicopy gene element. Samples with the highest parasite load (assessed using quantitative PCR) were selected for PCR-restriction fragment length polymorphism (PCR-RFLP) targeting the surface antigen 3 (SAG3), SAG2 (5’ and 3’), beta-tubulin (BTUB) and dense granule protein 6 (GRA6) loci, and the apicoplast genome (Apico). Toxoplasma gondii DNA was detected in all three of the populations sampled, presenting 30.6, 31.3 and 25.3% occurrence in free-range chickens, pigs and seropositive pregnant women, respectively. Quantitative-PCR indicated low parasite occurrence in most positive samples, limiting some further molecular analyses. PCR-RFLP results suggested that T. gondii circulating in the sampled populations presented with a type II genetic background, although all included a hybrid type I/II or II/III haplotype. Concatenation of aligned RFLP amplicon sequences revealed limited diversity with nine haplotypes and little indication of host species-specific or spatially distributed sub-populations. Samples collected from humans shared haplotypes with free-range chickens and/or pigs. Africa remains under-explored for T. gondii genetic diversity and this study provides the first detailed definition of haplotypes circulating in human and animal populations in Nigeria.     

Blood groups and affective disorders

Frequencies of ABO, Rh, MNSs, P, Kell, Lewis and Duffy blood groups were studied in a total of 219 patients with affective disorders. The patients were classified into four groups: (1) bipolar (manic-depressive) psychosis; (2) unipolar recurrent depressive psychosis; (3) nonpsychotic 'reactive' depression, and (4) 'unclassifiable'. The following statistically significant results were found: an increased frequency of the blood group factor B among psychotic (bipolar and unipolar) patients compared to nonpsychotic patients, a decreased frequency of the SS phenotype in the unclassifiable group and an increased frequency of the K(+) phenotype among the nonpsychotic patients. Previous results concerning differences between bipolar and unipolar patients with respect to the A and O blood types were not confirmed in this investigation.     

Genetics of human populations of Caucasus: distribution of various immunological and biochemical markers in eastern Georgia

The distribution of genetic markers of blood groups (AB0, P, Rhesus, MNSs, Duffy, Lewis, Kell-Cellano), of the serum proteins (Hp, Gc, Tf, C'3), red-cell enzymes (AcP, EstD, GLO1) and also ABH-secretion among seven native populations of Eastern Georgia has been studied. The frequencies of genes and haplotypes were calculated for the polymorphic markers and the results obtained were used in analysis of interpopulation variation and genetic relationship of these populations to their geographical neighbours as well as to European and West Asian populations.     

Genetics of the native inhabitants of the Caucasus: distribution of various immunological and biochemical markers in North Osetiia and Checheno-Ingushety

The distribution of genetic markers of blood groups (AB0, Rhesus, MNSs, P, Duffy, Kell-Cellano), plasma proteins (Hp, Gc, C'3, Tf) and red-cell enzymes (Glo-1, AcP, EstD, 6-PGD, PGM1) as well as ABH-secretion has been studied among 6 native populations of North Osetia and Checheno-Ingushety. Distribution of gene frequencies in populations of North-Osetians, Chechenians, Ingushians and other Caucasian ethnic groups was comparatively studied.     

Polymorphism C3435T of the MDR1 gene in Central Americans and Spaniards

The human multidrug resistance gene (MDR1) encodes for P-glycoprotein (P-gp) which is a transmembrane transporter protein that acts as an efflux pump for a number of lypophilic compounds. It plays a protective role for cells against DNA damage. The wobble C3435T polymorphism at exon 26 has been associated with different expression levels and activity. Differences in allele frequency of the C3435T polymorphism have been demonstrated between distinct ethnic groups. In our study we examined these polymorphisms in 433 healthy individuals. From these, 229 were Central American mestizos from Nicaragua (n = 117) and El Salvador (n = 112) to be compared with a group of 204 North Spaniards, with the aim of detecting potential genotypic differences between these populations. The genotypes were determined by PCR-RFLP. The frequencies of the C allele were very similar among Central Americans (0.53) and Spaniards (0.52), which is consistent with the ethnic origin of Central American individuals (Amerindians and European Caucasians). In comparison to other previously studied populations, the C allele frequency in Central Americans was significantly lower than that found in African populations and higher than that observed in the Indian and Southwest Asian populations. These data may be relevant for dose recommendation of P-gp substrate drugs and also for studies of allele disease association in the Central American population.     

格列美脲与沙格列汀联合治疗对2型糖尿病患者血糖控制、胰岛素抵抗及血脂的影响

目的:探讨2型糖尿病(T2DM)患者经格列美脲联合沙格列汀治疗后的临床效果,并分析其对患者血糖控制、胰岛素抵抗及血脂的影响。方法:选取我院2017年4月~2019年4月期间接收的88例T2DM患者,按乱数表法将患者分为研究组(n=44,格列美脲联合沙格列汀治疗)、对照组(n=44,沙格列汀治疗)。比较两组患者临床疗效、血糖、胰岛素抵抗及血脂指标,记录两组患者不良反应情况。结果:研究组治疗3个月后临床总有效率较对照组升高(P<0.05)。两组患者治疗3个月后空腹血糖(FBG)、餐后两小时血糖(2hPBG)、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、甘油三酯(TG)均下降,且研究组低于对照组(P<0.05)。两组患者治疗3个月后高密度脂蛋白(HDL-C)、空腹胰岛素(FINS)升高,且研究组高于对照组(P<0.05)。两组不良反应总发生率比较无差异(P>0.05)。结论:T2DM患者采用格列美脲联合沙格列汀治疗效果确切,可改善机体血脂水平及胰岛素抵抗,控制血糖水平,且用药安全性较好。     

Duffy antigen/receptor for chemokines (DARC): genotypes in Ashkenazi and non-Ashkenazi Jews in Israel.

Duffy genotypes were studied in Ashkenazi and non-Ashkenazi groups in Israel. The prevalence of the genotypes for the known polymorphic FY*A, FY*B, and FY*B(GATA-) alleles was similar in the two groups. The recently described FY*B(G298A) and FY*B(C265T) alleles were also found to be polymorphic. FY*B(G298A) was significantly more prevalent in the non-Ashkenazi group than in the Ashkenazi group (in 20% and 10% of FY*B, respectively). FY*B(C265T), which markedly diminishes the expression of Fy(b) antigen, was found in 3.5% of FY*B alleles, but only together with FY*B(G298A), consistent with previous suggestions that FY*B(C265T) occurred in the FY*B(G298A) allele. No difference in Duffy genotype distribution was found between schizophrenic and control groups. Duffy antigens are receptors for chemokines and bind Plasmodium vivax. Study of Duffy genotypes in additional populations might help in elucidating the possible functional significance of Duffy allele polymorphism.     

Genetics of Caucasian population: distribution of various immunological and biochemical markers in western Georgia

The distribution of genetic markers of blood groups (ABO, Rhesus, MNSs, P, Duffy, Kell-Cellano), plasma proteins (Hp, Gc, Tf, C'3) and red-cell enzymes (AcP, EstD, GLO-1), and also ABH secretion among 10 populations of Western Georgia has been studied. The common characteristic of distribution of gene frequencies for the markers studied was obtained as a whole in Georgia. The Georgians were compared for these markers with some populations of the Caucasus, Europe and West Asia. Among Caucasian populations, Georgians are most similar to Abkhasians. According to some systems, Georgians are close to European groups (ABO, Dubby, GLO-1, EstD), while they are similar to West-Asian groups, as judged by other systems (ABH secretion, AcP). According to Rhesus and MNSs systems, Georgians differ both from populations of Europe and from populations of West Asia.     

Genotype and mating type analysis of Cryptococcus neoformans and Cryptococcus gattii isolates from China that mainly originated from non-HIV-infected patients

Cryptococcosis has been reported to be mostly associated with non-HIV-related patients in China. However, little is known about the molecular characteristics of clinical isolates from the Cryptococcus neoformans species complex in this country. In this study, 115 clinical isolates were included. Molecular type VNI was the most representative ( n =103), followed by VGI ( n =8), VNIII ( n =2), VNIV ( n =1), and VGII ( n =1). With the exception of a serotype D mating type a isolate, all possessed the MAT α locus. Multilocus sequence typing (MLST) revealed that most Cryptococcus gattii isolates from China shared identical MLST profiles with the most common MLST genotype reported in the VGI group, and the only one VGII isolate resembled the Vancouver Island outbreak minor genotype. The C. gattii strains involved in this study were successfully grouped according to their molecular type and mating types by PCR-restriction fragment length polymorphism (RFLP) analysis of the GEF1 gene. Our results suggest that (1) in China, cryptococcosis is mostly caused by C. neoformans var. grubii (molecular type VNI), and mating type α; (2) The most common causative agents of C. gattii infection in China are closely related to a widely distributed MLST genotype; and (3) The PCR-RFLP analysis of the GEF1 gene has the potential to identify the molecular and mating types of C. gattii simultaneously.     

Linkage of hereditary motor and sensory neuropathy type I to the pericentromeric region of chromosome 17.

Vance et al. have reported linkage of hereditary motor and sensory neuropathy type I (HMSN I) to the pericentromeric region of chromosome 17. We have studied eight families with HMSN I (also called the hypertrophic form of Charcot-Marie-Tooth disease) for linkage of the disease locus to polymorphic loci in the centromeric region of chromosome 17. Linkage has been confirmed for D17S58 (EW301) with a maximum lod score of 5.89 at theta = 0.08 and for D17S71 (pA10-41) with a maximum lod score of 3.22 at theta = 0.08. EW301 is on 17p, 5.5 centimorgans from the centromere. Two families, previously reported as being linked to the Duffy blood group locus on chromosome 1, were included in this study, and one now provides positive lod scores for chromosome 17 markers. There was no evidence of heterogeneity.     

Genetic studies in four populations of the northern Aegean Sea, Greece

A total of 945 non-related individuals from four isolated population groups from the Northern Aegean Sea (Greece)--Alonissos, Oxilithos, Skopelos, and Glossa, has been typed for 16 polymorphic systems of the blood, namely A1A2B0, MNS., Rhesus (C, c, Cw, D, E, e), Kell, Duffy (a,b), Kidd (a); Hp, Tf subtypes, Gc, Gm (1, 2, 3, 5, 13), Km (1); aP, AK, PGM1, EsD, and 6-PGD. The distribution of phenotype and gene/haplotype frequencies shows a considerable interpopulational variability, which is discussed considering the history of these populations as well as the impact of locally acting microevolutionary factors such as drift and founder effects. The average coefficient of gene diversity GST comes to 0.0147, whereas Wahlund's variance is on average 0.0154, and Wright's Fst = 0.0147. Genetic distance analysis reveals a pattern of similarities, which is in conformity with the history of the populations under study.     

Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband

To determine the impact of a family history of the common form of type 2 diabetes and the phenotype of the proband on anthropometric and metabolic variables in normoglycemic first-degree relatives, we studied 2,100 first-degree relatives of patients with the common form of type 2 diabetes (FH+) and 388 subjects without a family history of diabetes (FH-). All subjects participated in an oral glucose tolerance test to allow measurement of insulin secretion [30-min incremental insulin/glucose (I/G 30)] and insulin sensitivity [homeostasis model assessment (HOMA) of insulin resistance (IR)]. A subset participated in a euglycemic clamp (n = 75) and an intravenous glucose tolerance test (n = 300). To study the effect of a particular phenotype of the proband, insulin secretion and sensitivity were also compared between first-degree relatives of diabetic probands with high and low waist-to-hip ratio (WHR) and probands with early and late onset of diabetes. FH+ subjects were more insulin resistant, as seen from a higher HOMA-IR index (P = 0.006) and a lower rate of insulin-stimulated glucose uptake (P = 0.001) and had more features of the metabolic syndrome (P = 0.02, P = 0.0002) compared with FH- subjects. Insulin secretion adjusted for insulin resistance (disposition index, DI) was also lower in the FH+ vs. FH- subjects (P = 0.04). Relatives of diabetic probands with a high WHR had reduced insulin-mediated glucose uptake compared with relatives of probands with a low WHR (P = 0.04). Relatives of diabetic patients with age at onset <44 yr had higher HOMA IR (P < 0.005) and lower DI (P < 0.005) than relatives of patients with age at onset >65 yr (highest quartile). We conclude that early age at onset of type 2 diabetes and abdominal obesity have a significant influence on the metabolic phenotype in the nondiabetic first-degree relative.     

13/17罗伯逊易位猪POU1F1基因多态性

采用外周血淋巴细胞培养制备染色体标本, 对13/17罗伯逊易位猪的3种杂交组合的394头后代进行核型分析, 出现3种核型猪：13/17易位纯合子猪[2n=36, XY或XX, rob(13;17)]、13/17易位杂合子猪[2n=37, XY或XX, rob(13;17)]和正常核型猪[2n=38, XY或XX]。应用PCR-RFLP技术在POU1F1基因的1 746 bp扩增片段中检测到1个RsaⅠ限制性内切酶的多态位点。应用PCR-SSCP技术检测POU1F1基因第4外显子, 在3种杂交后代群中均未检测到突变。遗传多态性分析结果表明：RsaⅠ酶切多态位点的突变在3种杂交后代群中A等位基因和AA基因型频率占优势, 在3种核型群体中也是A等位基因和AA基因型频率占优势, 其中AB基因型频率在易位杂合型群体中较高。各杂交后代群均未达到Hardy-Weinberg平衡, 不同核型群亦处于非平衡状态。13/17易位杂合子猪×13/17易位杂合子猪和13/17易位杂合子猪×约克两杂交后代群的PIC表现为中度多态, 而13/17易位杂合子猪×皮杜杂交后代群表现为低度多态; 易位杂合型群体表现为中度多态, 正常核型和易位纯合型群体表现低度多态性。