Northern Indian Population Research Articles

Prevalence and species spectrum of both pulmonary and extrapulmonary nontuberculous mycobacteria isolates at a tertiary care center

Objective/background: Nontuberculous mycobacteria (NTM) infection associated with pulmonary and extrapulmonary disease has been increasing globally. Despite an increase in incidence rate of NTM infection, its prevalence, species diversity, and circulation pattern in India is largely unknown. This study sought to investigate the overall burden and diversity of NTM among both pulmonary and extrapulmonary clinical isolates from a Northern Indian population. Methods: The study was conducted in the Department of Microbiology, from January 2013 to December 2015. A total of 4620 clinical samples were collected from patients suspected to have pulmonary and extrapulmonary tuberculosis. Preliminary diagnosis was performed using Ziehl–Neelsen staining followed by liquid culture in BacT/ALERT three-dimensional system. A total of 906 positive cultures obtained were differentiated as either NTM or Mycobacterium tuberculosis complex using a biochemical and MPT64 antigen test. Further identification of NTM species was confirmed with a line probe assay. Results: Out of 906 cultures isolates, 263 (29.0%) were confirmed as NTM and 643 (71.0%) were identified as Mycobacterium tuberculosis complex. A total of 79.4% of the NTM were recovered from pulmonary and 18.2% from extrapulmonary specimens. The diversity of NTM species was high (13 species) and predominated by Mycobacterium abscessus (31.3%) followed by Mycobacterium fortuitum (22%), Mycobacterium intracellulare (13.6%), Mycobacterium chelonae (9.1%), however, M. abscessus and M. fortuitum were the predominant species in both types of clinical isolates. Men (60.4%) and older patients aged greater than 55years were the predominated risk group for NTM infection. Conclusion: The high prevalence and species diversity of NTM suggests the need for immediate and accurate characterization of NTM for proper treatment and management of patients.

Association of NOD1 and NOD2 polymorphisms with Guillain-Barré syndrome in Northern Indian population

BackgroundNucleotide oligomerization domain (NOD) proteins are cytosolic pattern recognition receptors that respond to bacterial substrate and induce NF-κB activation in host. Association of NOD polymorphisms have been studied in many autoimmune disorders, however its role in Guillain-Barré syndrome (GBS) remains unknown. We have investigated NOD1 Glu266Lys and NOD2 (Arg702Trp and Gly908Arg) gene polymorphisms among patients with GBS. Materials and methodPolymorphisms in NOD-1 (Glu266Lys) and NOD-2 (Arg702Trp and Gly908Arg) genes were studied using polymerase chain reaction-restriction fragment length polymorphism in 105 patients with GBS and 100 healthy controls. ResultsHomozygous genotype (Lys/Lys) of NOD1 was significantly associated with GBS (p=0.013); and its subtypes viz. acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) (p=0.008 and p=0.024 respectively) than controls. In NOD2 (Arg702Trp and Gly908Arg) polymorphisms, only heterozygous genotype (Arg/Trp and Gly/Arg) showed significant association with GBS (p=0.001 and p=0.01 respectively); subtypes AMAN, acute motor-sensory axonal neuropathy (AMSAN) and AIDP showed association with heterozygote Arg702Trp (p=0.001; p=0.029 and p=0.001 respectively) whereas only AIDP was associated with heterozygote genotype Gly908Arg (p=0.003). ConclusionNOD1 (Glu266Lys) and NOD2 (Arg702Trp and Gly908Arg) polymorphisms were associated with an increased susceptibility to GBS. These polymorphisms could be genetic marker to GBS susceptibility.

Knockdown Resistance (kdr) Mutations in Indian Anopheles stephensi (Diptera: Culicidae) Populations.

Knockdown resistance (kdr) in insects resulting from mutation(s) in the voltage-gated sodium channel (VGSC) gene is one of the mechanisms of resistance against DDT and the pyrethroid group of insecticides. Earlier, we reported the presence of two classic kdr mutations, i.e., L1014F and L1014S in Anopheles stephensi Liston, a major Indian malaria vector affecting mainly urban areas. This report presents the distribution of these alleles in different An. stephensi populations. Seven populations of An. stephensi from six states of India were screened for the presence of two alternative kdr mutations L1014F and L1014S using allele-specific polymerase chain reaction assays. We recorded the presence of both kdr mutations in northern Indian populations (Alwar and Gurgaon), with the preponderance of L1014S, whereas only L1014F was present in Raipur (central India) and Chennai (southern India). None of the kdr mutations were found in Ranchi in eastern India and in Mangaluru and Mysuru in southern India. This study provides evidence for a focal pattern of distribution of kdr alleles in India.

Estimation of Height from Measuring Foot , Hand and Head Length in Northern Indian Population

Estimation of Height from Measuring Foot , Hand and Head Length in Northern Indian Population

Death receptor 4 variants enhanced prostate cancer risk in North Indian population.

Death receptor 4 (DR4) is a tumor suppressor gene and plays an important mediator of apoptosis. Polymorphism in DR4 gene may reduce apoptotic capacity and provoke proliferation of cell and cancer. We evaluated genetic polymorphisms of DR4 gene in association with risk of prostate cancer (PCa) in Northern Indian population. We have recruited 192 PCa patients and 225 cancer-free ages matched unrelated healthy control of similar ethnicity. They were genotyped for DR4, 141 (G > A), 209 (C > G), and 228 (A > C) polymorphisms using amplification refractory mutation system (ARMS) method. Variant genotype AA (OR = 2.54; p = 0.007) and A allele (OR = 1.51; p = 0.015) of DR4 141 demonstrated significant increased risk for PCa. Similarly, variant genotype GG (OR = 2.58; p = 0.003) and G allele carrier (CG + GG) (OR = 1.50; p = 0.043) of DR4 209 conferred increased risk. G allele (OR = 1.50, p = 0.005) was also statistically associated with PCa risk. High risk for PCa was also observed with respect to haplotypes A-G-A (OR = 2.86; Bonferroni correction Pc = 0.008) and A-G-C (OR = 3.18, Pc = 0.008). We observed significantly enhanced risk for PCa due to interaction between DR4 209 and 228 gene polymorphisms. Furthermore, a significantly increased risk of high Gleason grade tumor was found in the combined variant allele carrier (GA + AA) of DR4 141 compared with the GG genotype (OR = 2.27, Pc = 0.052). Interaction of smoking and genotypes did not further modulate the risk of PCa. Our observations suggested that genetic variants of the DR4 gene significantly influence the risk of PCa in North Indian population and might be involved in the etiology of PCa.

Palatal Rugoscopy: A new era for forensic identification

Aims and Objectives: To observe and compare the distribution of various palatal rugae patterns in western and northern Indian populations and to study the variations in male and female subjects respectively. Materials and Methods: The study consisted of 100 subjects, 50 each from the two groups of geographically different regions of western and northern India. After obtaining informed consent, an alginate impression of maxillary arch was made for interpretation. The number, type, and unification were followed according to Thomas and Kotze's classification and the shape was recorded according to Kapali et al.'s classification. Results: The shape of rugae was compared between the two study groups and was found to be highly significant between western Indian and northern Indian subjects. The number and shape of rugae differed significantly between the genders, with males having a highly significant difference as compared to the females. The western Indian group showed wavy shape predominantly in males and females had straight rugae. Similarly, the northern Indian male participants also had wavy shape; however, females in this group had more curved shaped rugae. Conclusion: The uniqueness of palatal rugae pattern can be utilized similar to fingerprints and when combined with other methods, it can help in the identification of a person.

Comment to "Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer".

To the Editor, The article by Colagar et al. [1], in the latest issue of this journal, showed the relationship between the genetic polymorphism of vitamin D receptor (VDR), as a VDR polyA allele L microsatellite variants, serum level of 25(OH)D3 and risk of breast cancer. As in many other type of malignancies, low levels of 25(OH)D3, the main circulating form of vitamin D following dietary intake, has been associated with higher breast cancer susceptibility, particularly with plasmatic levels of 25(OH)D3 below 20 to 32 ng/mL [2]. Therefore, one of the major goal pursued by physicians endeavoured to prevent or fight cancer is to increase plasma bioavailability of 25(OH)D3 by increasing vitamin D intake or ameliorating its gut adsorption, supplementation protocol or pharmacokinetics [3]. However, the paper by Colagar appears to raise the same concern that I addressed in some recent papers of mine [4], namely that the preventive effect of vitamin D on cancer depends on the wide collection of factors including genetic polymorphism for VDR [1], for example, for breast cancer the different ability of individuals to respond to 1,25(OH)2D3 might depend on the Taq1 VDR polymorphism [5]. The individual genetic endowment to respond to vitamin D, in such a fashion able to assess its presumptive chemopreventive potential against some important malignancies such as breast cancer, should be a fundamental hallmark to arrange any vitamin D supplementation protocol [4]. Other genetic polymorhisms may be involved in the chemopreventive role of 25(OH)D3, for example those ones regarding P450 family of cytochromes [6], as interestingly CYP1A1 is involved in xenobiotic metabolism and is a VDR target [7], moreover CYP3A4 is a human microsomal 25(OH)D3 hydrolase [8]. Because of the genetic variability of VDR exising within the Causasian population, the authors discussed the controversial issue that any variant in VDR may influence the activity of vitamin D against tumors and their prevalence in the population [1]. Yet, some correlation exists between low levels of circulating 25(OH)D3 and frequency of breast cancer [2,9], which should suggest for an increase in vitamin D intake as a supplementation aid, but very few reports correlated positive outcomes for breast cancer incidence following vitamin D supplementation [3,10]. While several papers associated cancer risk with a low 25(OH) D3 plasma level, the reason of this insufficient bioavalailability is far to be elucidated. Cancer cells can promote the 25(OH) D3 enzymatic hydroxylation, contribuiting in the reduction of the level in the circulating form [11,12], The protective effect against breast cancer claimed by the authors [1] might derive from a wide panoply of variability, which may even involve P450 cytochromes and aryl hydrocarbon receptor polymorphism [13,14], though some contradictory evidence yet exists [15]. The conclusion which the authors reached assessed that breast cancer risk is related to low levels of the circulating metabolite 25(OH)D3 and to a favorable assessment of a VDR genetic polymorphism, particularly with poly(A) long (LL+LS) microsatellite alleles [1]. Interestingly, this genetic polymorhism was associated with breast cancer also in a Northern Indian population, nearby the Iranian regions from which the authors recruited their patients [16]. Interestingly, Fok1 polymorphism is a poly(A) microsatellite polymorphism, which was recently closely associated to breast cancer [17], although yet Fok1 is also a VDR polymorphism that has been associated with many other types of cancers [18] and even with pulmonary tuberculosis susceptibility [19]. The authors did not clarify which kind of VDR polymorphism, previously described in the literature, they reported in their paper. The genetic association of VDR polymorphism to several types of cancer makes particularly puzzling the role of the genetic variability of vitamin D enzymes and receptors in the presumptive chemopreventive role of 1,25(OH)2D3. HLA-aplotype genetic linkage may be a possible path to focus onto vitamin D action on tumors. Due to the strong association with tuberculosis (TB) susceptibility and Fok1 VDR polymorphism [19], a suggestion might come from the evidence that some HLA alleles, such as the aplotypes HLA-DRB1, HLA-DQB1 or more precisely DRB1*1101-1121-DQB1*05 are associated with TB as well as the polymorphic SNP variants Fok1, Bsm1, Apa1, and Taq1, some of which related to breast cancer [20]. The question is if some HLA aplotypes in linkage disequilibrium with VDR polymorphic genes may be used as genetic markers to evaluate the individual's vitamin D response against breast cancer [21]. This issue puts questions and concerns about the fundamental role of genetic determinants for ensuring vitamin D efficacy in counteracting cancer malignancy through its immune modulating and hormonal action.

A community-based study to assess the awareness of health insurance among rural Northern Indian population

Background : Even after more than 60 years of independence, inequalities in access to health care are widely prevalent in Indian communities. As per National Family Health Survey-3 only 5% household are covered under any health scheme or insurance. Objectives : The present study was planned to conduct with an objective to assess the awareness of health insurance among rural northern Indian population. Materials and Methods : The present cross-sectional survey was undertaken among 422 eligible subjects in the rural field practice area of Department of Community Medicine of a Tertiary Care Centre located in rural Uttar Pradesh, during June 2013 to August 2013. Results : Overall 44.5% of the study subjects were aware of health insurance, while remaining 55.5% had not heard about it. Gender wise males were more aware than females (51.3% vs. 32.4%). Participants belonging to higher socioeconomic class were more aware (67%) compared to those of the lower class. A good number of respondents believed that health insurance is for tax gain (35.30%) and coverage of medical expenses (41.23%). 77.4% of respondents believed in governmental health insurance agencies rather than private insurance companies. Conclusion : The findings of the study highlight that it is need of the hour to launch information, education and communication activities in order to make rural communities aware of the need of health insurance to meet the ever rising medical expenses in view of unpredictable illness and injuries.

Effects of schizophrenia risk variation in the NRG1 gene on NRG1-IV splicing during fetal and early postnatal human neocortical development.

Neuregulin 1 (NRG1) is a multifunctional neurotrophin that mediates neurodevelopment and schizophrenia risk. The NRG1 gene undergoes extensive alternative splicing, and association of brain NRG1 type IV isoform expression with the schizophrenia-risk polymorphism rs6994992 is a potential mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain tissue. The authors investigated the temporal dynamics of transcription of NRG1-IVNV, compared with the major NRG1 isoforms, across human prenatal and postnatal prefrontal cortical development, and they examined the association of rs6994992 with NRG1-IVNV expression. NRG1 type I-IV and NRG1-IVNV isoforms were evaluated with quantitative real-time polymerase chain reaction in human postmortem prefrontal cortex tissue samples at 14 to 39 weeks gestation and postnatal ages 0-83 years. The association of rs6994992 genotype with NRG1-IVNV expression and the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms were also determined. Expression of NRG1 types I, II, and III was temporally regulated during prenatal and postnatal neocortical development. NRG1-IVNV was expressed from 16 weeks gestation until age 3. Homozygosity for the schizophrenia risk allele (T) of rs6994992 conferred lower cortical NRG1-IVNV levels. Assays showed that NRG1-IVNV is a novel nuclear-enriched, truncated NRG1 protein resistant to proteolytic processing. To the authors' knowledge, this study provides the first quantitative map of NRG1 isoform expression during human neocortical development and aging. It identifies a potential mechanism of early developmental risk for schizophrenia at the NRG1 locus, involving a novel class of NRG1 proteins.

Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population.

Recent genome-wide association studies (GWAS) have identified variants in phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal squamous cell carcinoma (ESCC) in Chinese population. Although few studies have replicated this findings in other populations, but results are contradictory. So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population. The genotyping of PLCE1 variants were performed in 293 histopathologically confirmed incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and ethnicity-matched controls using PCR RFLP. All statistical analyses were performed through SPSS version 15.0. Modeling and functional prediction of two non-synonymous variants were carried out using bioinformatics tools. PLCE1 polymorphisms were not associated with susceptibility to ESCC or its clinical phenotypes (tumor location/lymph node metastasis). No interaction with environmental risk factors was found. In silico analysis suggested negligible effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT genotype conferred adverse outcome to ESCC patients. Our study for the first time suggests that GWAS originated PLCE1 variants do not have independent role in susceptibility of ESCC in northern Indian population; however, a novel haplo-tagging SNP rs7922612 may modify survival outcome of ESCC patients.

A study of Craniospinal Imaging in Patients with Anorectal Malformation

Introduction: Anorectal malformations are commonly associated with craniospinal abnormalities like hydrocephalus, tethered cord syndrome, occult spinal dysraphism, syringomyelia, meningomyelocele and Arnold Chiari malformation. Aim of our study was to identify the incidence of craniospinal anomalies in patients with anorectal malformation and to analyse utility of Ultrasound and MRI as a screening tool in these patients to detect such anomalies. Material and Method: 52 infants male and female of anorectal malformation were included. All underwent ultrasonography of brain and spinal cord and 27 patients underwent MRI to detect craniospinal anomalies. Result: Out of 52 cases 38(73.07 %) were males and 14(26.93 %) were females. High type ARM (34.61 %) and Vestibular fistulas(19.23 %) were most common type in male & female child respectively. On ultrasonography in this series no craniospinal abnormality was found. On ultrasonography subarachnoid space was normal in all cases and central canal diameter was found <1cm in all cases. No abnormalities were detected in posterior fossa like cistermagna dilatation, dilated ventricles, Chiari Malformation. MRI spine was done 27 patients with high and low type malformation, but no abnormality was detected. Conclusion: Craniospinal anomaly and tethered cord are not frequently found in patients with anorectal malformation, in Northern Indian Population. As no association was found between craniospinal anomalies and anorectal malformation in the present study, the use of Ultrasonography and MRI as a screening tool is not recommended unless clinically indicated.

Killer immunoglobulin like receptor gene content diversity among Northern Indian population

Background: Genes encoding KIR receptors are clustered in one of the most variable regions of the human genome. KIR gene frequencies vary in worldwide populations and reveal high probability of individuals differing in their gene content.Aim: This study aimed to investigate KIR diversity among the northern Indian population who share features with either Western Eurasian or East Asian populations. It sought to decipher how northern Indians are associated phylogenetically with global populations whilst also focusing on differentiation of populations.Subjects and methods: This paper studied 867 northern Indians using PCR-SSP. Gene and genotypic frequencies were calculated, using statistical analyses. Findings were compared against 76 global populations of differing ethnicities.Results: This northern Indian population shared characteristics with Western Eurasian or Asian Indian populations, as is evident from genetic distance, clustered heatmap, phylogenetic assessment and principal component analysis. The findings are consistent with the demographic history of northern India, including specific features, such as presence of comparatively high KIR B-haplotype as compared to A-haplotype.Conclusion: KIR frequencies and profiles of northern Indians were more similar to Western Eurasians, Africans and Asian Indians. This may suggest that KIR genes are under constant evolutionary pressures and selection, which may be linked to different invading pathogens.

Dental age estimation by Demirjian′s and Nolla′s method: A comparative study among children attending a dental college in Lucknow (UP)

Introduction: Estimation of age is an important aspect of forensic science. The assessment of age is useful in forensic odontology and in treatments plans of orthodontic and pedodontic patients. Aims and Objectives: The aim of the study was to determine dental age from orthopantomograph using Demirjian's method and Nolla's method. It was also to evaluate the interrelationship between chronological and dental age according to both these methods and to evaluate which technique was better. Materials and Methods: The study was conducted in the Department of Oral Medicine and Radiology of Babu Banarasi Das College of Dental Sciences (UP, Northern India). A total of 300 subjects (150 girls and 150 boys) of age group from 6 years to 15 years were enrolled. These subjects were grouped by a difference of 1 year into 10 groups (each group comprised of 30 subjects: 15 males and 15 females). For every individual included in the study a panoramic radiograph was taken, with standard parameters and adequate protective measures. Results: The results imply that Demirjian's method is applicable to all age groups and for both genders with better accuracy than Nolla's method, which had a limited utility in younger age group. Thus Demirjian's method is a better method when compared to Nolla's method in Northern Indian population.

Clinical presentation of various thyroid lesions in a study population attending a teaching hospital in North India

Background: The present study is undertaken to evaluate the different clinical presentations of thyroid lesions in Northern Indian population. Clinical examination, although very accurate in most cases of thyroid lesion, is inadequate in some areas especially, in staging of thyroid malignancies and in detecting the multi-nodularity of the gland. Methods: The study was conducted in the postgraduate department of pathology of a teaching hospital for a period of 1 year. It was a prospective hospital based Study. In each case, a brief clinical history and physical examination along with evaluation of relevant investigation was carried out. Patient was explained about whole of the procedure &amp; the consent for the procedure was taken in all patients. FNAC of thyroid gland was done and the results of FNAC were correlated with histopathology, wherever available. The final results were correlated with different clinical presentations using SPSS 11.5 software. Results: Out of the 139 patients, 134 presented with swelling in the neck, 3 patients presented with pain in the neck while as 2 patients came with discomfort in the neck. 74 patients have duration of swelling more than 2 years, 51 patients have duration upto 1 year, 10 patients have duration between 1 to 2 years and 4 patients have less than one month. Out of 139 patients, 110 patients have solitary swelling, 87 have swelling on right side, 119 presented with regular margins, 91 presented with firm consistency, 130 were mobile and 135 presented with non-tender. Conclusion: Majority of the patients presented after 2 years of illness i.e. 74. Only 4 patients presently acutely within 1 month of illness. The major complaint was swelling in neck i.e. in 134, rest presented with local pain and discomfort .

Association of Common Polymorphisms in TNFA, NFkB1 and NFKBIA with Risk and Prognosis of Esophageal Squamous Cell Carcinoma

BackgroundTumour necrosis factor-alpha (TNF-α) and nuclear factor of kappa light chain gene enhancer in activated B cells (NF-κB) play critical role in carcinogenesis processes like tumour initiation, proliferation, migration and invasion. Single nucleotide polymorphisms in TNF-α, NF-κB and its inhibitor IκB genes were shown to be associated with susceptibility and prognosis of several cancers; however, their role in esophageal squamous cell carcinoma (ESCC) is not well recognised. Therefore, in present study, we aimed to investigate association of common polymorphisms in TNFA, NFkB1 and NFKBIA with risk and prognosis of ESCC in northern Indian population. MethodsWe genotyped 290 ESCC patients (including 162 followed up cases) and 311 mean age, gender and ethnicity matched controls for TNFA -308G>A, NFkB1 -94ATTG ins/del and NFKBIA (-826C>T and 3’UTRA>G) polymorphisms using PCR alone or followed by RFLP and TaqMan assay.Results TNFA -308GA genotype was associated with increased risk of ESCC specifically in females and in patients with regional lymph node involvement, while, NFKBIA -826CT+TT genotype conferred decreased risk of ESCC in females. Haplotypes of NFKBIA -826C>T and 3’UTRA>G polymorphisms, C-826G3’UTR and T-826A3’UTR, were associated with reduced risk of ESCC. No independent role of NFkB1 -94ATTG ins/del polymorphism in susceptibility of ESCC was found. Multi-dimensionality reduction analysis showed three factor model TNFA-308, NFKBIA-826, NFKBIA 3’UTR as better predictor for risk of ESCC. Furthermore, combined risk genotype analysis of all studied polymorphisms showed increased risk of ESCC in patients with 1-3 risk genotype compared to ‘0’ risk genotype. Survival analysis did not show any significant prognostic effect of studied polymorphisms. However, in stepwise multivariate analysis, metastasis was found to be independent prognostic predictor of ESCC patients.Conclusion TNFA-308 and NFKBIA (-826C>T and 3’UTRA>G) polymorphisms may play role in susceptibility but not in prognosis of ESCC patients in northern Indian population.

COX‐2 gene polymorphisms and risk of chronic periodontitis: a case–control study and meta‐analysis

Cyclooxygenase-2 (COX-2) enzyme is a major mediator of inflammation in periodontitis, leading to loss of gingival tissues and alveolar bone supporting the teeth. Previous studies have explored the role of COX-2 polymorphisms with the risk of periodontitis in different ethnic groups; however, findings are inconsistent. So, we aimed to investigate the association of COX-2 polymorphisms (rs20417, rs689466, and rs5275) in susceptibility to chronic periodontitis (CP) in northern Indian population. Meta-analysis was also carried out to precisely estimate the effect of COX-2 polymorphisms in CP. Genotyping of COX-2 polymorphisms was carried out through PCR-RFLP in 200 CP cases and 200 controls. For risk estimation, binary logistic regression was applied using SPSS, version 15.0, while meta-analysis was carried using MIX 2.0 software. None of the COX-2 polymorphisms independently were associated with the risk of CP. Meta-analysis suggested a significant reduced risk of CP with rs5275+8473 C allele and rs20417 in Chinese population. No association was observed in any of the studied COX-2 polymorphisms with CP in North India. But, the study should be replicated in larger sample size to arrive at a definitive conclusion. Meta-analysis suggested a role of rs5275 COX-2 polymorphisms in susceptibility to overall CP, and on ethnic basis, rs20417 showed reduced risk of CP in Chinese population.

Prognostic Significance of K-ras Codon 12 Mutation in Patients with Resected Gallbladder Cancer

Background: Point mutation of K-ras is associated with carcinogenesis and overall survival in various cancers. We investigated the mutational spectrum of K-ras codon 12 in resected normal and gallbladder cancer tissue samples in a Northern Indian population and correlated it with different clinicopathological parameters. Patients and Methods: Gallbladder tissues from normal (n = 24) and cancer patients (n = 39) were analyzed for K-ras codon 12 mutation by restriction fragment length polymorphism. Statistical analysis was carried out using the χ² test or Fisher's exact test. Survival was estimated using the Kaplan-Meier method, and the difference between survival curves was analyzed by the log-rank test. Results: The frequency of K-ras mutation was significantly higher (p = 0.001) in gallbladder cancer tissue samples (16/39) compared to normal samples (1/24). Patients with K-ras mutation had a significantly decreased overall survival (p = 0.003), particularly for stage II (p = 0.021) and III (p = 0.009) cancers. No significant correlation was observed with any of the other clinicopathological factors studied. Conclusions: Gallbladder cancer has a high frequency of K-ras codon 12 mutation with poorer outcomes in resected stage II and III disease. K-ras mutational analysis has important prognostic implications that need to be investigated further.

Associations of CYP1A1, GSTM1 and GSTT1 Polymorphisms with Lung Cancer Susceptibility in a Northern Indian Population

Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. This might be a factor in the variation in lung cancer incidence with ethnicity. We conducted a case-control study of 218 northern Indian lung cancer patients along with 238 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of Lung cancer in our population. We observed a significant difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=1.87, 95%CI: 1.25-2.80-0.73, P=0.002). However, GSTM1 null genotype was found associated with lung cancer in the non-smoking subgroup. (P=0.170). Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.

Mupirocin resistance in clinical isolates ofStaphylococcus aureusin a tertiary care hospital set up in North India

Background: Mupirocin is a topical antibiotic used for nasal decolonisation of methicillin resistant Staphylococcus aureus (MRSA). While resistance to mupirocin has been described it is usually not tested for in most clinical laboratories. Aim: The present study was carried out to detect the occurrence of mupirocin resistance in clinical isolates of Staphylococcus aureus in a tertiary care hospital set up in northern India. Materials and Methods: Staphylococcus aureus isolates obtained from clinical samples received in the microbiology laboratory over a period of one year were included in this study. Mupirocin resistance was detected by three phenotypic methods; disk diffusion method using 5μg and 200μg mupirocin disk to determine low-level and high-level resistance, broth microdilution method and an agar dilution method for determining minimum inhibitory concentrations. Methicillin sensitivity was also determined in the study isolates. Results: Of 250 non-duplicate Staphylococcus aureus isolates obtained, 5 (2%) were found resistant to mupirocin. All mupirocin resistance isolates were shown to have high-level resistance (minimum inhibitory concentration > 512μg/ml). All mupirocin resistant isolates were also resistant to methicillin. Results obtained by all three phenotypic methods showed good correlation. Conclusion: High-level mupirocin resistance is present in the northern Indian population which may be of major concern to prevent the spread of MRSA in hospitals and community.

Prevalence of HIV Drug Resistance Mutation in the Northern Indian Population After Failure of the First Line Antiretroviral Therapy

There is limited information available about the prevalence and pattern of human immunodeficiency virus (HIV) drug resistance mutations (DRMs) among antiretroviral therapy (ART) experienced patients from northern India. Results of genotypic drug resistance testing were obtained from plasma samples of 128 patients, who had presented with clinical or immunological failure to treatment after at least six months of ART. Major DRMs associated with any of the three classes of antiretroviral (ARV) drugs, nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI), were seen in 120 out of 128 patients (93.8% prevalence). NRTI and NNRTI DRMs were each seen in 115/128 (89.8%) patients, with M184V, M41L, D67N and T215Y being the most frequent among NRTI associated mutations, and K103N, G190A, Y181C and A98G among NNRTI associated ones. PI DRMs were observed in 14/128 (10.9%) patients, with L10I, V82A and L89V being the commonest. These results present a high prevalence of DRMs among ART experienced patients from northern India with clinical or immunological failure of therapy. It emphasizes the need for regular testing of plasma samples of such patients for DRMs in order to detect and replace a failing regimen early, and also the use of HIV drug resistance genotyping of ART naive individuals prior to initiating first line ART for possible transmitted resistance. It is very important to enhance the access of patients to ARV drugs so that their compliance could be improved and hence development of DRMs be minimized.