166 32nd World Congress of Internal Medicine (October 24-28, 2014) WCIM 2014
PS 0463 Genetics
Combined Effects of Thyroglobuline Polimorphisms with HLA-DR Locus and Gender Factor in Graves’ Disease
E. Sacide KOZAN1, H. Ilke ONEN2, Salih KOZAN3, Yalcin ARAL4, Ahmet YILDIRIM4, Mesut AKYOL5, Zafer Aydin ECEMIS6, Necat IMIRZALIOGLU7
Yildirim Beyazit University, Health Science Faculty, Turkey1, Gazi University, Medicine Faculty, Turkey2, Gulhane Military Medicine Academy, Turkey3, Ankara Education and Research Hospital, Turkey4, Yildirim Beyazit University, Medicine Faculty, Turkey5, Ankara Education and Research Hospital, Turkey6, HRS Women Health Hospital, Turkey7
Background: Etiology of autoimmune thyroid diseases (AITD), including Graves’ dis- ease (GD) and Hashimoto thyroiditis (HT) is multifactorial with female dominance.
Thyroglobuline (TG) among thyroid specifi c genes and DR locus of human leukocyte antigen (HLA) encoding genes among immune specifi c genes were reported as fi rst candidate loci in their own groups. However, distribution results of polymorphisms both in TG and HLA-DR in different ethnic backround have been shown incompatible Methods: Two hundred twenty one samples, consisting of 140 AITD (70 GD and 70 HT) patients and 70 controls were included to the study. Single nucleotide polymorphisms (SNPs) in TG: rs180223, rs2069550, rs853326, rs853303 and rs2076740 were analysed by PCR-RFLP and sequenced in 20 samples for confi rmation. Linkeage-disequilibrium were analysed between included SNPs. In fi nal step, determined risk-containing factors were evaluated with DRB1*15 (detected in previous study) and gender in GD.
Results: T,T genotype of rs2076740 were signifi cantly higher in controls than AITD patients (p=0.038). There were remarkable differences of GD with both HT patients and controls (p=0.033) for rs853326. A,G genotype were decreased in GD patients in comparition with controls (OR: 2.389) and HT patients (OR=2.591). G,G genotype were dramatically decreased in HT patients in comparition with GD (OR: 2.591). Sequences of amplifi ed region of TG SNPs were compatible with RFLP Results: Strong linkeage between rs180223, rs2069550 and rs853326 were also detected. In combination of A,G genotype absence for rs853326 with DRB1*15 and being female were shown in increasingly rise from single factor to more factors in GD in comparision with controls.
Conclusions: Analysis of combined effects of TG SNPs with HLA-DR locus and gender factors might be seen more benefi cial in stead of single succestibility allele determina- tion for predisposition of GD..
PS 0465 Genetics
A Study on XRCC1, P53 Gene Polymorphisms in Pa- tients with Hepatocellular Carcinoma (HCC) in South- ern India
Vellingiri BALACHANDAR1,2, Subramaniam MOHANA DEVI2, Meyyazhagan ARUN2, S HARIPRIYA2, Iyer MAHALAKSHMI1, SN DHARWADKAR3, Keshavarao SASIKALA2 Human Molecular Genetics Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, India1, Human Molecular Genetics Laboratory, Department of Zoology, Bharathiar University, India2, KLE University, India3
Background: Hepatocellular carcinoma (HCC) ids one of the most common cancer worldwide. Polymorphism in p53 and XRCC1 genes were associated with increased risk of early-onset HCC. We thus hypothesized that, these polymorphism could be more likely in South Indian population. However the status of these mutations in South In- dian HCC had not been studied.
Methods: In the present study 130 HCC patients and 130 control subjects were ana- lyzed for known polymorphisms in the p53 and XRCC1 genes.
Results: In the Arg194Trp polymorphism of p53 gene, we found 19.05% with Arg- 399Trp (heterozygous variant) genotype and 1.6% with 399Trp (homozygous var- iant) in comparison to controls who exhibited 90.39% with wild type genotype. In Arg399Gln polymorphism of XRCC1 gene, 46.17% were found to have Arg399Gln (heterozygous variant) genotype and 10.11% were found to have 399Gln (homozy- gous variant) genotype in comparison to controls who exhibited 55% individuals with heterozygous variant genotype and 16.75% with homozygous variant genotype. This polymorphic incidence revealed signifi cant association with advanced stages of the HCC and also well differentiated tumor.
Conclusions: Thus the results of our study provide the genetic variations of p53 and XRCC1 which may contribute to the susceptibility to HCC in South India. The results suggest that, these genes could play a signifi cant role in HCC and the combined effect of these variants may interact to increase the risk of HCC in Indian population.
PS 0466 Genetics
Role of Gene GSTp1 in the Development of Predisposi- tion to Allergic Asthma in Uzbek Population
Shukhrat Khudayberdiyevich ZIYADULLAEV1, Nazira Musaevna KHAITOVA1, Tamara Uktamovna ARIPOVA2, Musa M KHAYDAROV1
Samarkand State Medical Institute, Uzbekistan1, Institute of Immunology, Academy of Sciences of the Republic of Uzbekistan, Uzbekistan2
Important gene-candidate asthma is a gene of enzymes biotransformation xenobiotics - GSTp1, expressing almost exclusively in lung tissue. This gene is located in locus 11q13, for which repeatedly show adhesion to atopic symptoms. The purpose of the study was to establish the distribution of allele and genotype frequencies of poly- morphic variant gene GSTp1 patients allergic asthma and to establish a “negative”
combination leading to the development of the disease in the Uzbek population. The distribution of allele and genotype frequencies of polymorphic variant gene GSTp1 in patients with asthma. The diagnosis was verifi ed in accordance with the diagnostic criteria GINA-2006. Material for investigation, DNA samples of patients with asthma and healthy Uzbek people. Analysis of the polymorphic variant gene GSTp1 carried out by PCR of DNA synthesis on a thermocycler and RFLP analysis using primers Forward - 5’-GTA GTT TGC CCA AGG TCA AG-3 ‘Reverse - 5’-AGC CAC CTG AGG GGT AAG -3 ‘and subsequent detection of the restriction fragments by electrophoresis in a 6%
polyacrylamide gel. In the analysis of allele frequencies Ile-105/Val-105 polymorphism gene GSTp1 found that Ile105 allele in patients allergic asthma is more common than in the group of healthy individuals (80% opposite 65%). The study of polymorphism genotypes shows that in patients with allergic asthma frequency of the homozygous variant Ile105Ile gene signifi cantly higher than the control group of healthy individuals (62% opposite 30%). Thus, the results of molecular genetic studies have demonstrat- ed the importance of a polymorphic variant of the gene GSTp1, the formation of the genetic structure of the predisposition to allergic asthma in the Uzbek population. The fi ndings suggest that markers of increased risk of allergic asthma in people of Uzbek ethnicity are genotype GSTp1-Ile105Ile and allele GSTp1-Ile105.
PS 0467 Genetics
Quality of Life in Patients with Hereditary Hemorrhagic Telangiectasia
Cristina Maria ELIZONDO1, Carla SCARANO1, Constanza FRANCESCHINI1, Nora Angelica FUENTES1, Hernan Diego Giunta1, Liliana ROJAS1, Marcelo Martin SERRA1 Hospital Italiano De Buenos Aires, Argentina1
Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic disorder that affects 1/5000-8000 individuals worldwide. It is characterized by recurrent epistaxis, mucocutaneous telangiectasias and arteriovenous malforma- tions (AVMs) in organs such as lung, liver, central nervous system (CNS) and gastro- intestinal tract (GI); their clinical manifestations and possible complications added, frequently alters quality of life of these patients.
Objective: To identify associated factors with lower quality of life in adult patients with HHT.
Methods: Cross-sectional study, from 2010 to 2013, of prospectively evaluated pa- tients, from the institutional registry of HHT at Hospital Italiano, Buenos Aires. Quality of life (QoL) was measured with the EuroQol and visual analog scale (AVS) validated for the country. Presence of epistaxis, anemia, AVMs in CNS, lung, liver, GI tract, symptoms and related complications were evaluated.
Results: 127 patients were included: 33% were men, with a median age of 47 years (IQR:16). Median for QoL measured by the VAS was 69 (ICR:20.3). From the total, 96,1% presented epistaxis, from which 33,9% had severe epistaxis; 60% had anemia, 65,15% pulmonary AVMs, 39,4% were symptomatic; 19,6% had AVMs in CNS; 73,5%
had hepatic AVMs and 63% had GI AVMs from which 27,6% presented symptoms.
Signifi cant association was found between de median of QoL measured by VAS with:
anemia (62 vs. non-anemic 77.8, p=0.001), pulmonary AVMs (62.3 vs. 71.27 without pulmonary AVMs, p=0.056), hepatic AVMs (64.67 vs. 78.15 without AVMs, p=0.012), GI AVMs (60 vs. 70 without AVMs, p=0.043) and correlation coefficient age was -0.349 age (p<0.001).
Conclusions: Factors associated to decrease QoL in HHT were anemia and hepatic, pulmonary and GI AVMs. There was no difference in QoL related to epistaxis, but this could be attributed to the low number of patients without epistaxis.
