Higher Frequency In Cases Research Articles

Abstract POSTER-BIOL-1348: No association between PARK2 and BRCA1-associated gynecologic cancers

Abstract Purpose of study: We sought to identify genomic modifiers of gynecologic cancer penetrance in BRCA1 185delAG mutation carriers. In a pilot study using the Illumina 610K Quad chip to perform a whole genome analysis of 592,532 single nucleotide polymorphisms (SNP), we found significant SNP genotype differences in the PARK2 gene between BRCA1 185delAG mutation carriers who developed gynecologic cancer (cases) compared to those who did not (controls). These SNPS created a haplotype structure that was present at four-times higher frequency in cases than controls (37% vs. 9%, p=0.0009). We hypothesized that PARK2, which has been shown to be mutated in other cancers and to have a tumor suppressive function, plays a role in the biology of BRCA1-associated gynecologic cancer development. Experimental Procedures: To validate a PARK2 risk haplotype in an independent dataset, we isolated germline DNA from 85 BRCA1 185delAG mutation carriers and used TaqMan SNP Genotyping to genotype seven SNPs in PARK2. To determine whether a correlation exits between the PARK2 risk haplotype and PARK2 expression levels in tissue, we quantified PARK2 expression in normal ovaries and ovarian cancer tissue using quantitative real-time PCR (qPCR). To determine the rate of PARK2 mutations in 17 BRCA1-associated ovarian cancers, we used a touchdown PCR protocol to amplify and sequence each PARK2 exon. To identify exon deletions and duplications in the PARK2 gene, we utilized the multiplex ligation-dependent probe amplification (MLPA) technique. Summary of Data: In an independent dataset of 85 BRCA1 185delAG mutation carriers, we found the PARK2 risk haplotype to be present in 35 (17%) of cases. The risk haplotype was present in a higher proportion of cancer cases than benign controls (6/12 or 50% vs. 29/73 or 8%), but this was not significant (p=0.54). We did not find a difference in PARK2 ovarian tissue expression levels in patients with and without the PARK2 risk haplotype. We sequenced the PARK2 gene and performed MPLA analysis from tumor DNA of 17 ovarian cancers from BRCA1 185delAG mutation carriers, but did not identify any deleterious PARK2 mutations or exon deletions and duplications. Conclusions: We did not validate a PARK2 risk haplotype as a modifier of gynecologic cancer penetrance in BRCA1 185delAG mutation carriers. We did not find evidence for PARK2 inactivation in BRCA1-associated gynecologic tumors. Citation Format: Christine Walsh, Hoorig Nassanian, Hasmik Agadjanian, Carl Miller, Sandra Orsulic, Beth Karlan. No association between PARK2 and BRCA1-associated gynecologic cancers [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1348.

Genetics and environmental risk factors associated with febrile seizures

The aim of this study was to determine genetic and environmental risk factors associated with febrile convulsions among children in the United Arab Emirates. This study was based on matched case-control studies. Subjects were collected from the Al-Ain Medical Health District and the Tawam and Al-Ain Teaching Hospitals of Faculty of Medicine and Health Sciences. Seventy patients with febrile seizure were identified and were matched to 70 control febrile patients without seizure with the same age range (3-36 months), who attended the same hospitals during the same period of time. Mothers of studied patients and controls were interviewed by telephone. If the mother was not available, the father was interviewed. Potential risk factors were investigated. The mean and standard deviation for age were 17.0 ± 7.9 months for studied patients and 18.0 ± 9.1 months for controls. The highest frequency of cases with febrile seizure was in children aged 1-2 years. Forty six cases (65.7%) had a febrile seizure for the first time and 24 cases (34.3%) had it before (recurrent febrile seizure). The Mantel Haenszel test revealed that sex, respiratory infection, positive family history, and birth weight were significant predictors for febrile seizure. It is recommended to establish health educational programs for mothers regarding febrile seizures and how to deal with their children during such attacks.

Effect of TP53 16-bp and β-TrCP 9-bp INS/DEL polymorphisms in relation to risk of breast cancer

P53 as a tumor suppressor and an apoptosis modulator, is the regulator of the cell cycle and apoptosis, and contributes to mammary gland development and breast cancer (BC) progression. BTRC gene (Homo sapiens beta-transducing repeat containing E3 ubiquitin protein ligase) encoded protein, β-TrCP, is a novel regulator of p53. The current study aimed to assess the possible effects of TP53 IVS3 16bp (rs17878362) and β-TrCP 9bp (rs16405) INS/DEL polymorphisms on BC risk in an Iranian population. A total of 439 women including 236 BC patients and 203 healthy women were recruited. The TP53 and β-TrCP INS/DEL polymorphisms were genotyped by allele-specific polymerase chain reaction method. Our data demonstrated that the TP53 16-bp INS/DEL variation was associated with an increased risk of BC in codominant (INS/INS vs. DEL/DEL: OR=1.82; 95% CI=1.02–3.23; P=0.042) and dominant (Del/INS+INS/INS vs. DEL/DEL: OR=1.48; 95% CI=1.03–2.21; P=0.044) models. Additionally, the variant allele (INS) of TP53 DEL/INS polymorphism with a relatively higher frequency in cases than in controls (35.6 vs. 27.8) was a risk factor for BC (OR=1.43; 95% CI=1.06–1.93; P=0.017). With respect to β-TrCP INS/DEL polymorphism, our study failed to find any difference in allele and genotype distribution between BC patients and controls in codominant, dominant and recessive tested inheritance models (P>0.05). Furthermore, no significant association among the β-TrCP and TP53 genotype distribution and clinical characteristics of BC patients were found (P>0.05). Our findings suggest that the TP53 16-bp INS/INS and DEL/INS+INS/INS genotypes as well as the INS allele could be genetic factors related to BC risk.

Self-inflicted burns among Saudi Arabian soldiers

Background : Self-inflicted burns (SIB) are the most common and frequently occurring medical challenge to Plastic Surgery and Burn Units worldwide. Only a few reports of SIB among soldiers have been published; they may be committed as a coping mechanism to stress, psychiatric illness, or with a malingering/ulterior motive. The aim of this retrospectives study is to determine the cause and characteristic of the SIBs among soldiers treated at Burn Unit of Prince Sultan Military Medical City (PSMMC) during 2008-2014. Materials and Methods: A retrospective assessment was performed on 82 soldiers treated at Burn Unit of PSMMC for self-inflicted burn injuries. The data collected include age, cause of injuries, side of the body affected, affected organs, month and day of burn injury. Results : The majority of SIB was observed among young soldiers age range 20-35 years. The chemical burn was the most common cause of burn injuries. The SIBs mostly occurred between June and September months with a higher frequency of cases occurring in early weekdays. Most of the burns occurred in the feet and hands, left side of body suffered more burns compared to right side of the body. Conclusion : It may be concluded that chemically induced burns were the most frequent cause of SIB in this study. High frequency of SIB occurred in summer months specifically on Sundays and Mondays. Feet, hands, and legs are the most affected organs. The reason of inflicting self-injury is far from clear it may be either to cope up with stress or with an ulterior motive. Further investigation using the larger sample is suggested.

A Matrilineal Genetic Legacy from the Last Glacial Maximum Confers Susceptibility to Schizophrenia in Han Chinese

Mitochondrial dysfunction has been widely reported in schizophrenia patients. To dissect the matrilineal structure of Han Chinese with or without schizophrenia and to decipher the maternal influence and evolutionary history of schizophrenia, a total of 1212 schizophrenia patients and 1005 matched healthy controls, all of Han Chinese origin, were recruited in Hunan Province, China. We classified haplogroup for each individual based on mitochondrial DNA (mtDNA) sequence variations and compared the haplogroup distribution pattern between cases and controls. Haplogroup B5a presented a higher frequency in cases than in controls (P = 0.02, OR = 1.67, 95% CI = [1.09, 2.56]), and this result could be confirmed by permutation analysis. Age estimation of haplogroup B5a in cases revealed a much younger age than that of controls, which was coincident with the Northern Hemisphere deglaciation at the end of the Last Glacial Maximum. Analysis of complete mtDNA in five patients belonging to haplogroup B5a showed that this background effect might be caused by haplogroup-defining variants m.8584G>A and m.10398A>G. Our results showed that matrilineal risk factor for schizophrenia had an ancient origin and might acquire a predisposing effect on schizophrenia due to the environment change and/or orchestration with other nuclear genetic factors appeared recently in human evolutionary history.

Primary Cutaneous Neuroendocrine Carcinoma, Merkel Cell Carcinoma. Case Series 1991–2012

Introduction and objectivesMerkel cell carcinoma was first described by Toker in 1972. It is an uncommon, primary neuroendocrine skin carcinoma which appears in the dermoepidermic area, grows fast, is very aggressive and has a poor prognosis. The aim of this work is to highlight the importance of this tumour, which develops mainly in the skin of the head and neck area, and whose prevalence has increased in recent years. Material and methodWe gathered data on 16 patients suffering cutaneous neuroendocrine carcinoma treated at our hospital between September 12, 1991 and July 13, 2012. We indicated the age and gender of patients. We described the area where the tumour was located, indicating the size in millimetres, according to the major axis of the lesion. ResultsMost of the patients studied were over 70 years old, except for one who was 55. The highest frequency of cases appeared among patients aged over 80 years. In the cases studied, when the tumour appeared in the head and neck region (10/16), its location could be nasal-lateronasal, cheek-malar, upper eyelid, frontal or mandibular. The major axis of the lesion ranged between 7 and 35mm. Unlike with epidermoid or basocellular carcinomas, recurrence and ganglionar metastases were common. Immunohistochemical (CK20) tests are essential for a correct diagnosis. Treatment is usually surgical and occasionally followed by radiotherapy and chemotherapy. ConclusionThis carcinoma is not a very common skin tumour. It appears in old age, in the head and neck region in 50% of cases and often leads to exitus.

Carcinoma neuroendocrino primario de la piel, carcinoma de células de Merkel. Casuística 1991-2012

Introduction and objectivesMerkel cell carcinoma was first described by Toker in 1972. It is an uncommon, primary neuroendocrine skin carcinoma which appears in the dermoepidermic area, grows fast, is very aggressive and has a poor prognosis. The aim of this work is to highlight the importance of this tumour, which develops mainly in the skin of the head and neck area, and whose prevalence has increased in recent years. Material and methodWe gathered data on 16 patients suffering cutaneous neuroendocrine carcinoma treated at our hospital between September 12, 1991 and July 13, 2012. We indicated the age and gender of patients. We described the area where the tumour was located, indicating the size in millimetres, according to the major axis of the lesion. ResultsMost of the patients studied were over 70 years old, except for one who was 55. The highest frequency of cases appeared among patients aged over 80 years. In the cases studied, when the tumour appeared in the head and neck region (10/16), its location could be nasal-lateronasal, cheek-malar, upper eyelid, frontal or mandibular. The major axis of the lesion ranged between 7 and 35mm. Unlike with epidermoid or basocellular carcinomas, recurrence and ganglionar metastases were common. Immunohistochemical (CK20) tests are essential for a correct diagnosis. Treatment is usually surgical and occasionally followed by radiotherapy and chemotherapy. ConclusionThis carcinoma is not a very common skin tumour. It appears in old age, in the head and neck region in 50% of cases and often leads to exitus.

Perfil epidemiológico das infecções hospitalares por bactérias multidrogarresistentes em um hospital do norte de Minas Gerais

Backgound and Objectives: Nosocomial infection (IH) is an increasingly common problem and the presence of resistant microorganisms causes clinical and economic impact. This study aims to determine the epidemiology of nosocomial infections caused by Multidrug- Resistant bacteria in a hospital in northern Minas Gerais. Methods: Notifi cation forms obtained from the Infection Control Service (SCIH) of a hospital of Northern Minas Gerais were analyzed, for the period April 2011 to April 2012. Were included in the study all cases of Hospital Infection (IH) caused by multidrug- resistant bacteria (MDR). Results: There were 44 cases of MDR caused by IH, 19 females and 25 males. The most frequent infection sites were: Urinary Tract Infection (40,9%) and Bloodstream Infection (25%). The highest frequency of cases occurred in the age group 60 to 69 years and in the period 0-15 days of hospitalization. The bacteria found were Klebsiella pneumoniae (27.7%), Escherichia coli (23.4%), Acinetobacter baumannii (21.3%), Staphylococcus aureus (14.9%), Pseudomonas aeruginosa (6.4%), Enterobacter sp (2.1%), Morganella morganii (2.1%) and Burkholderia cepacia (2.1%). The resistance mechanism most frequent was ESBL production. IH by MDR has more invasive procedures that occur in bacteria IH not MDR, OR: 3.7 (95% CI: 2:02-4:03). Conclusion: The prevalence of MDR infection during the study period was 11.6%. It is important to detect and control the spread of MDR microorganisms because of their impact on morbidity and survival of patients. KEYWORDS: Hospital-Acquired Infection. Drug Resistance. Bacteria.

AB0001 Genetic polymorphism in GDF-5 gene as risk factor for development and progression of osteoarthritis

BackgroundThe etiological factors of osteoarthritis are not fully characterized though the pathology of osteoarthritis is well defined. Genome sequencing resulted in identification of several susceptibility loci confirming the genetic association...

Predictive factors in patients with advanced and metastatic squamous cell carcinoma of the head and neck: A study based on SWOG protocol S0420

To evaluate the prognostic values of different protein expression in the progression of squamous cell carcinoma of the head and neck (SCCHN) patients, we conducted immunohistochemical (IHC) analysis in tissue samples of different patients enrolled on SWOG protocol S0420. S0420 was a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent SCCHN. The primary end point was response probability, i.e., confirmed complete (CR) and partial response (PR). Sorafenib was administered orally at 400 mg twice daily on a continuous basis in 28-day cycles to eligible patients. Responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. IHC analysis was performed for various markers and data were analyzed statistically. IHC data were obtained from 19 patients enrolled on S0420. There was a high frequency of cases with expression of the angiogenesis markers SMA, HIF-1α, Raf-1, VEGF and VEGF-R. None of the markers were significantly associated with response. Negative HER-2 status was associated with longer progression-free survival (PFS), P=0.04. Negative NRP-1 status was associated with longer overall survival (OS), P=0.04. There were no other significant associations. An almost universal overexpression of angiogenesis markers in the samples analyzed supports the evaluation of angiogenesis inhibition as a potential target for therapy. High levels of NRP-1 and HER-2 in SCCHN samples appear to be associated with decreased survival and earlier progression of disease, respectively, in SCCHN patients and may represent targets for therapy.

Mitochondrial displacement loop alterations are associated with endometriosis

To evaluate the association of mitochondrial displacement (D-) loop alterations with endometriosis in south Indian women. Case-control study. Biochemistry and molecular biology laboratories. Women with (n = 152) and without (n = 150) endometriosis of south Indian origin. All women had a transvaginal ultrasound scan at screening followed by a laparoscopy to confirm the diagnosis (revised American Fertility Society stage III = 54; stage IV = 98). Genotyping of entire D-loop (1,124 bp) was carried out on genomic DNA of blood from cases and controls by polymerase chain reaction sequencing analysis. Twelve novel mutations and 187 reported polymorphisms were identified in the D-loop region of cases and/or controls. The A189G, 310 C insertion, T16189C polymorphisms, and 189G/310TC/16189C haplotype have significantly higher frequency in cases compared with controls. Mitochondrial D-loop alterations may constitute an inheritable risk factor for endometriosis. The analysis of D-loop alterations may help to identify patients at high risk for disease outcome.

Correction of Deformational Plagiocephaly in Early Infancy Using the Plagio Cradle Orthotic

The purpose of this study was to assess early treatment of deformational plagiocephaly using the Plagio Cradle, a modifiable cranial orthotic. Infants were included if they had treatment of deformational plagiocephaly with the Plagio Cradle beginning at 4 months or younger. Patients were prospectively stratified by the age treatment was initiated: group 1: under 10 weeks (n = 50); group 2: 10 to 20 weeks (n = 113). Pretreatment and posttreatment calvarial asymmetry was measured using direct anthropometry and reported as a transcranial difference (TCD). The end point for therapy was a TCD of 5 mm or less, falling within 2 SDs of published normative data. One hundred sixty-three infants were included. Initial TCD was significantly higher for group 1 as compared with group 2 (initial TCD: 11.0 vs 9.0 mm; P < 0.05). Duration of therapy was significantly longer for group 1 as compared with group 2 (6.9 vs 5.7 week; P < 0.05). Following cradle use, group 1 infants demonstrated a significantly larger change in TCD in comparison to group 2 (change in TCD: 6.0 vs 4.0 mm; P < 0.001). At the conclusion of therapy, group 1 infants trended toward greater calvarial symmetry than group 2 patients (final TCD: 4.5 vs 5.0 mm; P = 0.06) and a higher frequency of cases with full correction of asymmetry (62.4% vs 52.2%; P = 0.16). The Plagio Cradle can fully correct deformational plagiocephaly early in life. Nevertheless, treatment is more effective if initiated before 10 weeks of age.

Enteric viral infections as potential risk factors for intussusception

We aimed to identify potential risk factors for intussusception (ISS) among children presenting to two pediatric hospitals in Egypt. In this case-control study, enrolled children < 3 years old with ISS (confirmed radiologically and/or surgically) were matched by age and gender to controls admitted with acute non-abdominal surgical illnesses. Stool samples were collected and tested for various enteric bacteria, rotavirus, enteric adenoviruses (EA, 40 and 41) and astroviruses using commercially available ELISA diagnostic kits. From December 2004 to May 2009, 158 cases and 425 matched controls were enrolled. A history of diarrhoea and cough over the preceding four weeks of interview were more common in cases than controls, respectively. Children with mothers who had secondary education and above were 2.2 times more likely to have ISS than those whose mothers had a lower level of education. In spite of the low detection rate of EA infection (regardless of diarrhoea history) and asymptomatic rotavirus infection, they were detected in higher frequencies in cases than controls; however, infection with astrovirus and bacterial pathogens did not appear to be associated with increased risk of ISS. History of diarrhoea and cough over the four weeks preceding the study and maternal education above secondary level were potential risk factors for ISS. EA and asymptomatic rotavirus infection were detected in higher frequencies among cases than controls; however, association with ISS cannot be confirmed. Additional research is needed to confirm these findings and evaluate the pathogenesis which may link such infections with ISS.

The −174G/C and −572G/C Interleukin 6 Promoter Gene Polymorphisms in Mexican Patients with Rheumatoid Arthritis: A Case-Control Study

Objective. There is a lack of information about the genotype frequencies of IL-6 −174G/C and −572G/C polymorphisms in Mexicans with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the association of the IL-6 −174G/C and −572G/C polymorphisms in Mexican mestizo with RA. Methods. We included 137 patients with RA and 102 healthy controls. Patients were assessed for clinical characteristics. IL-6 −174G/C and −572G/C polymorphisms were genotyped using PCR-RFLP analysis. Allele and genotype frequencies and the Hardy-Weinberg equilibrium were computed. Odds ratios (ORs) were computed to identify the risk for RA associated with the presence of GG genotype in comparison with the GC or CC genotypes. Results. The genotype −174GG occurred at a higher frequency in cases and controls (77.4% versus 78.4%, P = 0.845). We found similar results for the genotype −572GG (54% in patients versus 60.8% in controls, P = 0.295). Conclusions. This is the first study to evaluate the association of −174G/C and −572G/C polymorphisms of the IL-6 gene with RA in Mexican mestizo patients. These two polymorphisms were not associated with RA in the studied sample. Additional studies are required to evaluate if these IL-6 polymorphisms have relevance to the development of more severe disease.

ASSOCIATION OF POLYMORPHISM IN GROWTH AND DIFFERENTIATION FACTOR 5 GENE WITH OSTEOARTHRITIS KNEE

The present study investigated to identify the association of polymorphism in GDF-5 gene with osteoarthritis in North Indian population. In a case-control study, 300 cases with knee osteoarthritis and an equal number of age and gender matched healthy controls were included. Cases were diagnosed using the ACR Guidelines of Knee Osteoarthritis (KOA). Clinical symptoms were assessed with the knee specific WOMAC index and VAS for knee pain. The severity of disease was determined by radiological KL grades (Kellgren Lawren). The variant genotype of GDF-5 was found to be present at significantly higher frequency in cases than in controls, resulting in about 1.79 fold increase in risk to OA. Genotype distributions of the GDF-5 also showed significant association of variant allele with clinical score of OA patients. An association between the+104T/C GDF5 polymorphism with knee OA and clinical symptom of OA in Indian population further demonstrate a strong genetic influence of this SNP in KOA.

1769 – Psychotic disorder and hospitalization through mobile crisis unit

Introduction The utility of Mobile Crisis Unit (MCU) and its target population has been a controversial issue and many scientific articles have been writen about it (1,2). Objective The aim of this study is to identify the demographic and clinical features of patients diagnosed with psychotic disorder who have been hospitalized and have not required hospitalization in psychiatric unit through a Mobile Crisis Unit (MCU). Methods We collected retrospectively demographic and clinical variables. These include psychiatric rating scales of severity: Clinical Global Impression Scale (CGI) and Psychiatric Disease Severity (GEP); of functionality as Global Assessment of Functioning Scale (GAF); the aggressive behaviour and violence scale (AVAT) and psychopathology with the Positive and Negative Syndrome Scale (PANSS) of a total of 136 patients between June 2007 and July 2010. Results There have been found stadisticaly significative differences between patients who have been hospitalized versus patients who have not in the items of treatment adherence and security staff intervention (Table 1). There is a positive correlation between patients who required hospitalization and the clinical scales CGI, GEP, GAF, AVAT, SUMD, PANSS-P and PANSS-G (Table 2). Conclusions We can conclude that patients cared for by the Mobile Crisis Unit (MCU) that require of psychiatric hospitalization have poor adherence to previous treatment. A high frequency of cases require intervention of security staff for having a higher risk of aggressiveness at the moment of hospitalization. The presence of greater psychopathology and functionality severity in patients hospitalized through the Mobile Crisis Unit (MCU) is also considered. Variables No hospitalization Hospitalization p N % N % Sex Men 33 54.1 41 54.7 0.95 Cohabitation Alone 15 24.6 25 33.3 0.27 Toxics Yes 14 23 17 22.7 0.97 Psychiatric history Yes 45 78.9 54 77.1 0.81 Previous hospitalizations Yes 42 68.9 42 56 0.12 Treatment adherence Yes 14 31.1 2 3.5 Security staff Yes 1 1.7 39 57.4 Chi-square Variables No hospitalization Hospitalization p Age 45,3(17,02) 45,44(16,16) 0,96 CGI 4,24(0,82) 5,11(0,67) GEP 12,09(4,18) 15,96(3,82) GAF 47,16(14,21) 37,07 (23,72) AVAT 2,41 (1,98) 4,15 (2,45) SUMD 10,65 (3,29) 12,97 (3,08) PANSS P 22,28(7,02) 28,79(6,43) PANSS N 21,89 (8,44) 20 (8,09) 0,19 PANSS PG 38,8 (9,51) 45,28 (9,65) Mean(SD)–T-test

Perfil epidemiológico dos acidentes ofídicos no Estado da Paraíba, Brasil, 2005 a 2010

Objective: to characterize clinical and epidemiological profile of snakebites in the state of Paraiba, Brazil, in the period 2005-2010. Methods: a cross-sectional descriptive study based on data obtained in the Information System for Notifiable Diseases, of the State Health Secretariat. Results: 3,033 cases were reported in the period, with an average of 505.5 cases/year; the annual incidence of the period was 13.7 cases per 100,000 inhabitants; the higher frequency of cases was in male gender (76.0%); the age group with highest risk was 60-64 years (18.9 cases per 100,000 inhab.); most cases occurred between May and August (43.1%) and the genus Bothrops (pit viper) caused most of these (83.0%); 122 were classified as severe cases (4.0%) and 18 (0.6%) died. Conclusion: months of greatest rainfall (May to August) presented highest number of cases; cure was the most common outcome; accidents of mild degree predominated.

Identification of genes involved in the initiation of osteoarthritis

Identification of genes involved in the initiation of osteoarthritis

Genetic polymorphism in GDF-5 gene as risk factor for development and progression of osteoarthritis knee

Purpose: In a case-control study, investigate the association of SNP in GDF- 5 gene with osteoarthritis knee Methods: In a case-control study, 300 cases with knee osteoarthritis and an equal number of age, gender matched healthy controls were included. Cases were diagnosed using the ACR Guidelines of knee osteoarthritis (KOA). Clinical symptoms were assessed with the knee specific WOMAC index and VAS for knee pain. The severity of disease was determined by radiological KL grades (Kellgren Lawren). The informed consent of the patients was obtained for the participation in this study. The study was approved by the Institutional Ethics Committee. The genomic DNA samples were isolated from blood and polymorphic study was done by polymerase chain reaction (PCR) with restriction fragments length polymorphism (RFLP). All statistical analysis was performed with the SPSS software package (version 16.0 for windows; SPSS Chicago, IL). Results: The GDF-5 (BSiE1) genotypes were found to be present at significantly higher frequency in cases than in controls, resulting in about 1.62 fold increase of OA risk (P Value=0.040). OA knee was found to be significantly associated with BMI (P Value=0.00). A significant association was found with clinical score of knee OA - VAS with poor and good index (P value=0.010 and 0.026 respectively) and in WOMAC with poor index only (P value=0.0040). On stratifying all osteoarthritis subjects into 3 groups according to severity (KL grade 2 minimal, grade 3 moderate and grade 4 severe OA), no significant association was found. Conclusions: GDF5, are now known to be consistently associated with the risk of knee OA, in different population. An association between the +104T/C GDF5 polymorphism with knee OA in Indian population further confirms a strong genetic influence of this SNP in KOA. This can serve as a potential biomarker and a risk factor for KOA. It may become a gateway for further research into epigenetic of this SNP, highlighting potential pathways for prevention and therapeutic intervention of knee osteoarthritis

Second‐trimester soft markers: relation to first‐trimester nuchal translucency in unaffected pregnancies

Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5(th) centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies.