Disease Markers - Volume 31, issue 5

Authors: Chatterjee, Arpita | Dutta, Samikshan | Sinha, Swagata | Mukhopadhyay, Kanchan

Article Type: Research Article

Abstract: Trisomy of the 21{st} chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2 ), located in the 21{st} chromosome were genotyped to understand their role in DS. …Genomic DNA of eastern Indian probands with DS (N=132), their parents (N=209) and ethnically matched controls (N=149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses. ETS2 rs461155 showed high heterozygosity in DS. Significantly lower frequency of SIM2 C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (P value =0.01669) and their fathers (P value=0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (P value =0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 'A' allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population. Show more

Keywords: Down syndrome, ETS2, SIM2, transcriptional regulation

DOI: 10.3233/DMA-2011-0825

Citation: Disease Markers, vol. 31, no. 5, pp. 247-257, 2011

Authors: Zidar, Nina | Boštjančič, Emanuela | Glavač, Damjan | Štajer, Dušan

Article Type: Research Article

Abstract: MicroRNAs are non-coding RNAs, functionioning as post-transcriptional regulators of gene expression. Some microRNAs have been demonstrated to play a role in regulation of innate immunity. After myocardial infarction (MI), innate immunity is activated leading to an acute inflammatory reaction. There is evidence that an intense inflammatory reaction might contribute to the development of ventricular rupture (VR) after MI. Using real-time PCR, we analysed the expression of miR-146a, miR-150, and miR-155 in autopsy samples of …infarcted heart tissue from 50 patients with MI (23 with VR and 27 without VR). An altered expression of all three microRNAs was found in MI compared to the normal hearts. Comparing MI patients with VR and those without VR, we found miR-146a up-regulation, and miR-150 and miR-155 down-regulation in patients with VR. In conclusion, our study demonstrated an altered expression of miR-146a, miR-150, and miR-155 in MI compared to the normal hearts. These microRNAs are involved in regulation of the innate immunity. Differential expression of these microRNAs in MI patients with VR in comparison to those without VR provides further evidence that innate immunity resulting in an intense inflammatory reaction plays an important role in the pathogenesis of VR after MI in humans. Show more

Keywords: Myocardial infarction, ventricular rupture, pathogenesis, inflammation, innate immunity, microRNA

DOI: 10.3233/DMA-2011-0827

Citation: Disease Markers, vol. 31, no. 5, pp. 259-265, 2011

Authors: Tóth, Réka | Fiatal, Szilvia | Petrovski, Beáta | McKee, Martin | Ádány, Róza

Article Type: Research Article

Abstract: The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary. The study included men, aged 45–64 years. Altogether, 241 cases with chronic liver disease (CLD) and 666 randomly selected controls without CLD were analysed for all four polymorphisms. Associations between the polymorphisms, individually, …and in combination, and excessive and problem drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage. The 272Gln/35Val allele increased the risk of excessive and problem drinking in homozygous form (OR=1.582, p=0.035, CI=1.034–2.421, OR=1.780, p=0.016, CI=1.113–2.848, respectively). The joint analysis showed that when combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is protective against CLD (OR=0.368, p=0.019, CI=0.159–0.851). The results obtained in the study help not only to clarify the effects of different ADH SNPs but to better understand how these polymorphisms modify each other's effects in the development of alcoholism and related diseases. Show more

Keywords: Genetic epidemiology, genetic, case-control study, alcohol, chronic liver disease

DOI: 10.3233/DMA-2011-0828

Citation: Disease Markers, vol. 31, no. 5, pp. 267-277, 2011

Authors: Mlakar, Simona Jurkovic | Osredkar, Josko | Prezelj, Janez | Marc, Janja

Article Type: Research Article

Abstract: Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis. The aim of the present study was to examine possible association of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in combination, with bone mineral density at femoral neck (BMD_fn), lumbar …spine (BMD_ls) and total hip (BMD_th) in Slovenian elderly women and men. GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence of GSTM1 and GSTT1 gene segments. BMD_fn, BMD_ls and BMD_th were measured by the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD_th, BMD_ls and BMD_fn values (p=0.031, 0.017 and 0.023, respectively) in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene deletion polymorphism borderline significant association was found with BMD_ls (p=0.100). Furthermore, subjects with homozygous deletion of GSTT1 gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion of GSTM1 gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association of GSTM1-null and GSTT1-null polymorphisms with BMD_ls values (p=0.044). Carriers with a combination of the presence of GSTT1 gene and the homozygous absence of GSTM1 gene fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD. Show more

Keywords: Osteoporosis, oxidative stress, antioxidant defence system, bone mineral density, triplex method, glutathione s-transferase

DOI: 10.3233/DMA-2011-0829

Citation: Disease Markers, vol. 31, no. 5, pp. 279-287, 2011

Authors: Gebril, Ola H | Meguid, Nagwa A.

Article Type: Research Article

Abstract: Background: Autism is among the commonest neurodevelopmental childhood disorders worldwide; its aetiology is still unknown. Iron metabolism alteration in the central nervous system is recently implicated as a risk factor for several neurodegenerative disorders. Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) have shown significant association with several neurological diseases. Some evidences show altered iron related proteins in serum of autistic children. The aim of this work is to conduct a preliminary pilot study for …the association of HFE polymorphisms and autism. Methods: All cases were referred from the clinic of special needs, National Research Centre, Cairo. Clinical diagnosis was based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls. Results: The p.H63D is more abundant than the C282Y among both autism and control samples. No significant association of p.H63D nor p.C282Y polymorphism and autism was revealed. Conclusion: We here report on the first pilot study of the possible genetic association between autism and HFE gene polymorphisms among Egyptians. Although our results do not prove the role of HFE polymorphisms as risk factors for autism, yet this does not exclude the role of iron in this prevalent disorder. Further extended studies are recommended to include other iron metabolism genes. Show more

Keywords: Neurodevelopmental disorders, Iron, haemochromatosis, genes, polymorphisms

DOI: 10.3233/DMA-2011-0830

Citation: Disease Markers, vol. 31, no. 5, pp. 289-294, 2011

Authors: Huang, Yuli | Hu, Yunzhao | Mai, Weiyi | Cai, Xiaoyan | Song, Yuanbin | Wu, Yanxian | Dong, Yugang | Huang, Huiling | He, Zhongyun | Li, Wensheng | Yang, You | Rao, Shaoqi

Article Type: Research Article

Abstract: Objectives: Oxidized low-density lipoprotein (ox-LDL) is considered to be a key factor of initiating and accelerating atherosclerosis. The objective of this study was to investigate the role of ox-LDL in young patients with coronary artery disease (CAD). Methods: 128 consecutive angiographically proven young CAD patients (aged ⩽ 55 years) were enrolled, and 132 age-matched non-CAD individuals (coronary angiography normal or negative finding by coronary ultrafast CT) were set as control group. Conventional risk …factors (hypertension, dyslipidemia, diabetes mellitus, obesity, smoking) were evaluated in the two groups. Ox-LDL was measured by competitive ELISA. Framingham risk score (FRS) and absolute 10-year CAD events risk were calculated for each individual. Results: Male sex was more prevalent in group CAD than in control (87.5% vs. 62.1%; P< 0.01). There were significant differences in smoking history (P< 0.01) and triglyeride (TG) and ratio of apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) (both P< 0.05) but no remarkable difference in other conventional risk factors (all P> 0.05) between group CAD and control. Level of ox-LDL was significantly higher in group CAD than in control (P< 0.01). Multivariate logistic regression showed that male sex (OR, 4.54; 95%CI, 1.76–9.77), smoking quantity (OR, 2.78; 95%CI, 1.34–4.25), TG (OR, 1.42; 95%CI, 1.18–2.83), ApoB/ApoA1 (OR, 1.73; 95%CI, 1.32–4.23), and ox-LDL (OR, 2.15; 95%CI, 1.37–6.95) were independently correlated with CAD in young patients. Area under the curve (AUC) of receiver operating characteristic (ROC) curve of TG, ApoB/ApoA1, and ox-LDL was 0.831, 0.866, and 0.935, respectively (P< 0.001). Conclusions: Ox-LDL is an important independent risk factor for CAD in young patients after adjusting other risk factors such as smoking, TG, and ApoB/ApoA1. Show more

Keywords: Risk factors, young, coronary artery disease, oxidized low-density lipoprotein

DOI: 10.3233/DMA-2011-0832

Citation: Disease Markers, vol. 31, no. 5, pp. 295-301, 2011

Authors: Chew, Constance S.N. | Cherry, Catherine L. | Kamarulzaman, Adeeba | Yien, Tan Hong | Aghafar, Zayd | Price, Patricia

Article Type: Research Article

Abstract: Objectives: Chemokines influence the migration of leukocytes to secondary lymphoid tissue and sites of inflammation. In HIV patients, they are implicated in inflammatory complications of antiretroviral therapy (ART), notably Immune Reconstitution Disease (IRD) and Sensory Neuropathy (SN). However most chemokines have not been monitored as patients begin ART or correlated with IRD and SN. Methods: Plasma chemokine levels were assessed longitudinally using commercial ELISAs in 69 patients treated in Kuala …Lumpur, Malaysia. Plasma was available at baseline and after 6, 12, 24 and 48 weeks on ART. Chemokine genotypes were assessed using allele-specific fluorescent probes. IRD were diagnosed in 15 patients. 30 patients were screened for SN using the ACTG BPNS tool after six months on ART. SN was detected in 8 patients. Results: Plasma CXCL10 levels decreased on ART compared to baseline (p=0.002–0.0001), but remain higher than healthy controls (p� 0.0001). The decline was clearer in patients without IRD. CCL5 levels rose on ART but remained similar to controls. CCL2 levels were higher in patients than controls after week 12. Plasma chemokine levels were not affected by CD4+ T-cell counts or any genotypes tested. Several patients with SN displayed higher CCL5 levels throughout therapy compared to patients without neuropathy. Levels of other chemokines and chemokine genotypes were not associated with SN. Conclusions: Chemokines are differentially affected by ART. CXCL10 and CCL5 may influence IRD and CCL5 warrants further investigation for an effect in SN. These trends are not influenced by chemokine genotypes investigated here. Show more

Keywords: HIV sensory neuropathy, nucleoside analogue reverse transcriptase inhibitor sensory neuropathy, CCL5, CXCL10, Immune Reconstitution Disease

DOI: 10.3233/DMA-2011-0844

Citation: Disease Markers, vol. 31, no. 5, pp. 303-309, 2011

Authors: Salem, Abdel Halim | Yaqoob, Alaeddin | Ali, Muhalab | Handu, Shailandra | Fadel, Raouf | Abu-Hijleh, Marwan | Almawi, Wassim

Article Type: Research Article

Abstract: Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated …healthy individuals. GSTM1 deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence of GSTT1 null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution of GSTM1 and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution of GSTM1 gene (P=0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addresses GST gene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and drug effects in Arab populations. Show more

Keywords: Glutathione S-transferase, genetic polymorphisms, Arabs

DOI: 10.3233/DMA-2011-0845

Citation: Disease Markers, vol. 31, no. 5, pp. 311-316, 2011

Authors: Kratz, Ewa M. | Faundez, Ricardo | K�tnik-Prastowska, Iwona

Article Type: Research Article

Abstract: Introduction: The aim of this study was to compare fucose and sialic acid residue expression on fibronectin and α _{1} -acid glycoprotein in the seminal plasma of men suspected of infertility and suffering from leukocytospermia. Subjects and methods: Seminal ejaculates were collected from 27 leukocytospermic and 18 healthy, normozoospermic men. The relative degree of fucosylation and sialylation of fibronectin and α _{1} -acid glycoprotein was estimated by ELISA using fucose and sialic …acid specific lectins from Aleuria aurantia, Lotus tetragonolobus, and Ulex europaeus as well as Maackia amurensis and Sambucus nigra, respectively. Results: Leukocytospermic seminal fibronectin, in comparison with fibronectin of normal fertile group, showed lower relative reactivity with AAL, LTA and UEA, and higher reactivity with MAA and SNA, while the AGP of the leukocytospermic group was less reactive with AAL, and the relative reactivity with LTA and MAA was significantly higher. Fibronectin and α _{1} -acid glycoprotein reactivity with UEA and MAA showed high positive correlations. Discussion: Leukocytospermia was associated with the alterations of terminal monosaccharide expression in human seminal fibronectin and α _{1} -acid glycoprotein. The increase of sialyl-Lewis^{\rm x} antigen in α _{1} -acid glycoprotein can be used as a marker of genital tract inflammation manifested by leukocytospermia. Show more

Keywords: Fibronectin, α _{1}-acid glycoprotein, fucosylation, sialylation, leukocytospermic human seminal plasma

DOI: 10.3233/DMA-2011-0846

Citation: Disease Markers, vol. 31, no. 5, pp. 317-325, 2011