Efficacy of pegylated Graphene oxide quantum dots as a nanoconjugate sustained release metformin delivery system in in vitro insulin resistance model.

Metformin, the primary therapy for type 2 diabetes mellitus (T2DM), showed limitations such as varying absorption, rapid system clearance, required large amount, resistance, longstanding side effects. Use of Nano formulations for pharmaceuticals is emerging as a viable technique to reduce negative consequences of drug, while simultaneously attaining precise release and targeted distribution. This study developed a Polyethylene Glycol conjugated Graphene Oxide Quantum dots (GOQD-PEG) nanocomposite for the sustained release of metformin. Herein, we evaluated the effectiveness of metformin-loaded nanoconjugate in in vitro insulin resistance model. Results demonstrated drug loaded nanoconjugate successfully restored glucose uptake and reversed insulin resistance in in vitro conditions at reduced dosage compared to free metformin.

Functional status of Indian children with juvenile idiopathic arthritis.

Background and Objectives: The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. Methods: A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Results: Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Conclusions: Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Homozygous GRHPR C.494G>A mutation is deleterious that causes early onset of nephrolithiasis in West Bengal, India.

Pediatric nephrolithiasis (NL) or Kidney stone disease (KSD) is an untethered topic in Asian population. In Western countries, the annual incidence of paediatric NL is around 6-10%. Here, we present data from West Bengal, India, on lower age (LA, 0-20 years) NL and its prevalence for the first time. To discover the mutations associated with KSD, twenty-four (18 + 6) rare LA-NL patients were selected for Whole Exome Sequencing (WES) and Sanger sequencing, respectively. It was found that GRHPR c. 494G>A mutation (MZ826703) is predominant in our study cohort. This specific homozygous mutation is functionally studied for the first time directly from human peripheral mononuclear cell (PBMC) samples. Using expression study with biochemical activity and computational analysis we assumed that the mutation is pathogenic with loss of function. Moreover, three genes, AGXT, HOGA1 and GRHPR with Novel variants known to cause hyperoxaluria were found frequently in the study cohort. Our study analyses the genes and variations that cause LA-NL, as well as the molecular function of the GRHPR mutation, which may serve as a clinical marker in the population of West Bengal, Eastern India.

ACE/ACE2 balance might be instrumental to explain the certain comorbidities leading to severe COVID-19 cases.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global catastrophe. The elderly and people with comorbidity are facing a serious complication of the disease. The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of angiotensin-converting enzyme (ACE) 2 (ACE2) receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. Here it has been discussed the role of interferon and protease during the receptor recognition (begining of infection) and followed by the impact of cytokine and hypoxia in the context of the balance of ACE/ACE2. It has also very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.

Induction of apoptosis in human bladder cancer cells by triterpenoids isolated from Holarrhena antidysenterica through differential reactive oxygen species generation.

A novel triterpenoid, holarol(1),3ß-lup-20(31)-en-3,29,30-triol along with one seco-triterpenoid, dihydrocanaric acid(2) and one known pentacyclic triterpenoid, betulin(3) have been isolated from Holarrhena antidysenterica (L.)Wall. (Family: Apocynaceae). The structures of the compounds were elucidated by extensive IR, 1D, 2D NMR and mass spectrometric analysis. The optimised geometry of (1) was calculated by density-functional theory (DFT) using M06-2X hybrid functional and 6-31 G(D) basis set. The compounds showed differential cytotoxic activities in the cell lines-HeLa, EAC, Raji and T24. Seco-triterpenoid (2) showed highest sensitivity (IC50: 1.710 µg/mL) against the bladder cancer cell line T24 followed by (1) (IC50 9.698 µg/mL) and (3) (IC50 11.769 µg/mL). Compound (1) showed highest reactive oxygen species (ROS) generation in T24 cell line followed by (3) and (2) resulting in induction of apoptosis through activation of caspase, cleavage of PARP and reduction of Bcl-2/Bax ratio. Thus compounds (1), (2) along with (3) could be potent anticancer agents.

Different Growth Responses to Recombinant Human Growth Hormone in Three Siblings with Isolated Growth Hormone Deficiency Type 1A due to a 6.7Kb Deletion in the GH1 Gene

Isolated growth hormone deficiency (IGHD) type 1A is a rare, autosomal recessive disorder caused by deletion of the GH1 gene and characterized by early onset severe short stature and typical phenotype. Lack of exposure to GH during fetal life often leads to formation of anti-GH antibody following exposure even the least immunogenic recombinant human GH (rhGH). Some patients with circulating anti-GH antibodies demonstrate lack of growth response to GH while others do not. However, the clinical significance of this antibody is unclear; hence testing is not routinely recommended. Three siblings, born of a consanguineous union, were referred with severe short stature. They were evaluated and IGHD was diagnosed in all of them. Genetic analysis revealed that all three had homozygous 6.7 Kb deletion in GH1 gene, while their parents displayed a pattern of heterozygous 6.7 Kb deletions. rhGH was started at 10, 6 and 1.58 years of age, respectively. Growth and hormonal parameters were monitored throughout the course of treatment. The eldest sibling demonstrated expected growth velocity (9.5 cm/year) for the first year of rhGH that rapidly waned thereafter (2.5 cm/year). The youngest sibling experienced excellent growth response even after the third year (10.3 cm/year) while the middle sibling displayed sub-optimal response from rhGH initiation (6.3 cm/year). Change of rhGH brand did not work in the two elder sisters. Such a different growth response with rhGH in three siblings harbouring similar genetic abnormality has not been described previously.

FSH ß-subunit mutations in two sisters: the first report from the Indian sub-continent and review of previous cases.

Isolated FSH deficiency due to mutations in the gene for ß-subunit of FSH is an extremely rare autosomal recessive disease of which only eleven cases have been reported so far. The clinical features include absent breast development and primary amenorrhea in females and azoospermia with normal testosterone levels in males. In this study we report two Kashmiri sisters born to native Kashmiri consanguineous parents with failure of onset of puberty. Hormonal evaluation revealed undetectable serum FSH and estradiol and high LH. Genetic analysis of FSH ß-gene identified one nonsense mutation (c.343C > T:p. Arg115Stop) in exon 3. The two sisters were homozygous for this nonsense mutation while the parents were heterozygous. Incorporation of a stop codon at 115 codon position is predicted to result in the formation of truncated FSH ß protein, lacking 14 amino acid from the carboxy-terminus (p.Arg115Stop). Very recently, this same mutation was reported for the first time in a Chinese male. Ours is the first ever report of any FSH ß-subunit mutation from the Indian sub-continent and this particular mutation in any female from anywhere in the world. We conclude and emphasize that this diagnosis should be considered in girls with delayed puberty and selective deficiency of FSH.

Association of Interleukin-1 beta and tumor necrosis factor-alpha genetic polymorphisms with gastric cancer in India.

Interleukin 1 beta (IL-1ß) and Tumor necrosis factor alpha (TNF-α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL-1ß and TNF-α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test. The study results revealed that IL-1ß rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30-2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67-3.83) and TNF-α rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54-3.46) polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that carriage of 7 "effective" risk alleles conferred a risk of almost 10-fold in comparison to individuals carrying less than 3 "effective" risk alleles. Our survival analysis also indicated a significant association between IL-1ß rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H. pylori enhanced the risk in individuals with IL-1ß rs1143627:CC and rs16944:TT genotypes. Further, meta-analysis revealed significant association of IL-1ß rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18-14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48-20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653-667, 2018. © 2018 Wiley Periodicals, Inc.

Association of FOLH1, DHFR, and MTHFR gene polymorphisms with susceptibility of Neural Tube Defects: A case control study from Eastern India.

BACKGROUND: Worldwide, Neural tube defects (NTDs) are considered as major clinical problems imposing a huge socio-economic burden for both affected individuals and their families. In India, the prevalence of Neural tube defects is significantly high. This study aims to evaluate the association between genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1 (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase (MTHFR) and neural tube defects from eastern India. METHODS: We enrolled 62 consecutive mothers with NTDs foetuses as cases and their corresponding age matched 73 mothers with healthy babies as controls (genetic power has been calculated). Four single nucleotide polymorphisms (FOLH1: rs202676, DHFR: rs70991108, MTHFR: rs1801133 and rs1801131) have been amplified by polymerase chain reaction (PCR) and sequenced. Statistical analysis has been undertaken to find out association with NTDs. RESULTS: Genotype and allele frequency analysis of these SNPs revealed that, rs1801133 (p.Ala222Val) was significantly associated with NTDs risk (p value = 0.028; odds ratio-2.31; 95% CI 1.08-4.93), whereas rs202676 (p.Tyr60His) showed protective role (p value = 0.0066; odds ratio-0.11; 95% CI 0.01-0.86). Serum homocysteine (Hcy) concentration was respectively higher in subjects carrying 222Ala/Val and 222Val/Val alleles (p value = 0.009; p value ≤ 0.0001). CONCLUSION: In conclusion, it can be stated that, rs1801133 was associated with neural tube defects risk in patients from the eastern part of India and it might be counted as a molecular marker for evaluating the susceptibility of NTDs.

Polymorphisms in ADH1B and ALDH2 genes associated with the increased risk of gastric cancer in West Bengal, India.

BACKGROUND: Gastric cancer (GC) is one of the most frequently diagnosed digestive tract cancers and carries a high risk of mortality. Acetaldehyde (AA), a carcinogenic intermediate of ethanol metabolism contributes to the risk of GC. The accumulation of AA largely depends on the activity of the major metabolic enzymes, alcohol dehydrogenase and aldehyde dehydrogenase encoded by the ADH (ADH1 gene cluster: ADH1A, ADH1B and ADH1C) and ALDH2 genes, respectively. This study aimed to evaluate the association between genetic variants in these genes and GC risk in West Bengal, India. METHODS: We enrolled 105 GC patients (cases), and their corresponding sex, age and ethnicity was matched to 108 normal individuals (controls). Genotyping for ADH1A (rs1230025), ADH1B (rs3811802, rs1229982, rs1229984, rs6413413, rs4147536, rs2066702 and rs17033), ADH1C (rs698) and ALDH2 (rs886205, rs968529, rs16941667 and rs671) was performed using DNA sequencing and RFLP. RESULTS: Genotype and allele frequency analysis of these SNPs revealed that G allele of rs17033 is a risk allele (A vs G: OR = 3.67, 95% CI = 1.54-8.75, p = 0.002) for GC. Significant association was also observed between rs671 and incidence of GC (p = 0.003). Moreover, smokers having the Lys allele of rs671 had a 7-fold increased risk of acquiring the disease (OR = 7.58, 95% CI = 1.34-42.78, p = 0.009). CONCLUSION: In conclusion, rs17033 of ADH1B and rs671 of ALDH2 SNPs were associated with GC risk and smoking habit may further modify the effect of rs671. Conversely, rs4147536 of ADH1B might have a protective role in our study population. Additional studies with a larger patient population are needed to confirm our results.

Absence of KCNQ4 mutation in Bengali families with ADNSHL originated from West Bengal, India.

OBJECTIVE: Autosomal Dominant Non-Syndromic Hearing Loss (ADNSHL) is extremely heterogeneous in nature. More than 60 loci with 30 different genes have been identified linked to ADNSHL. Mutation in KCNQ4 is considered as one of the most common causative factor responsible for ADNSHL. No study focused on the genetic alteration of KCNQ4 gene among hearing loss patients in India. The present study for the first time was carried out to determine the mutation spectrum of KCNQ4 gene in ADNSHL patients of West Bengal state, India. METHOD: Twenty nine individuals from 10 independent ADNSHL family (with two or more generation affected) were studied both clinically and genetically. Most of the patients showed moderate progressive sensorineural hearing loss. Mutation analysis was conducted for KCNQ4 gene using polymerase chain reaction followed by direct sequencing. RESULTS: Neither any reported nor a novel pathogenic mutation in KCNQ4was detected in our studied group, in contrast to the findings among East Asians. CONCLUSION: The result of the present study suggests that mutations in KCNQ4 gene are unlikely to be a major causative factor of ADNSHL in our studied patients from West Bengal, India, pointing to other genes might be responsible for ADNSHL in our studied patients.

Genetic Alterations in Pendrin (SLC26A4) Gene in Adult Hypothyroid Patients.

Current study was aimed to screen the SLC26A4 gene in 127 nonautoimmune and noncongenital hypothyroid patients, who were under optimal iodine nutrition and devoid of any characteristics of Pendred syndrome from eastern part of Indian population. 8 single nucleotide variants/mutations were identified in heterozygous state in 20% patient population, which include 1 novel nonsynonymous (p.C18S), 1 novel intronic (g.942C>A), 3 known nonsynonymous (p.S23X, p.V239D, and p.I455F), and 3 known intronic (g.23034G>T, g.29641C>G, and g.33893T>C) variants. Only g.23034G>T was noted also in homozygous state in 2% patient population. However, Controls exhibited only the variations g.23034G>T and p.I455F. Therefore, present study reports for the first time that the observed novel variants in pendrin gene might be linked with autoimmune negative hypothyroidism, without any characteristics of Pendred syndrome and/or congenital hypothyroidism. While, all observed known variants/mutations were reported with either Pendred syndrome and/or congenital hypothyroidism earlier, but never with nonautoimmune adult hypothyroidism solely. Thereby, the absence of any features of Pendred syndrome and/or congenital hypothyroidism in patients with observed known nonsynonymous variants/mutations may be due to either heterozygous state of each variant or differential domain specific activity of ions trafficking in the respective organ. The analysis of amino acid change at least for p.C18S, p.S23X, and p.V239D in correlation with phenotypic characteristics of respective patients might assume a possible effect on protein structure and function. Altogether, we report for the first time that genetical variations in SLC26A4 gene could play an important role in development of nonautoimmune adult hypothyroidism.

Association of calcitonin receptor gene (CALCR) polymorphism with kidney stone disease in the population of West Bengal, India.

Kidney Stone Disease (KSD) is a complex urologic disorder with strong genetic constituent. Earlier association studies have indicated that the genetic polymorphisms are the potential cause of stone materialization; however unfortunately, the actual genetic signature is still unknown. Therefore, present study was aimed to investigate the potential contribution of two important polymorphisms of calcitonin receptor gene (CALCR): (i) rs1801197 (Leu447Pro) and (ii) rs1042138 (3'UTR+18C>T) in renal stone formation. Accordingly, we enrolled 152 patients registered with calcium-rich stone in kidney (case) and 144 corresponding age, sex and ethnicity matched healthy individuals (controls). Epidemiological and clinical data were recorded as well as peripheral blood sample was collected from each individual. Serum creatinine and urinary calcium level was found high in patients, compared to controls. Out of two studied polymorphisms, we have not found any significant association against the rs1042138 with KSD, nonetheless, significant high frequency (p=0.001; Odds ratio=1.81; 95% CI: 1.28-2.55) of risk allele T against the rs1801197 (T>C) in patient was noted. Moreover, significant association with KSD was noted by genotypic analysis of rs1801197 (Leu447Pro) in our population. Interestingly, male patients carrying TT genotype was found to be at high risk of stone formation, while no such association was observed in female patients. Altogether, present study indicated that the rs1042138 might not be used as a useful marker for susceptibility of kidney stone formation, whereas, the rs1801197 could definitely be considered as one of the risk factors for KSD in Indian population at least in West Bengal in particular.

Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India.

Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95 % confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95 % CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95 % CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95 % CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.

No Polymorphism in Plasmodium falciparum K13 Propeller Gene in Clinical Isolates from Kolkata, India.

Molecular markers associated with artemisinin resistance in Plasmodium falciparum are yet to be well defined. Recent studies showed that polymorphisms in K13 gene are associated with artemisinin resistance. The present study was designed to know the pattern of polymorphisms in propeller region of K13 gene among the clinical isolates collected from urban Kolkata after five years of ACT implementation. We collected 59 clinical isolates from urban Kolkata and sequenced propeller region of K13 gene in 51 isolates successfully. We did not find any mutation in any isolate. All patients responded to the ACT, a combination of artesunate + sulphadoxine-pyrimethamine. The drug regimen is still effective in the study area and there is no sign of emergence of resistance against artemisinin as evidenced by wild genotype of K13 gene in all isolates studied.

Spectrum and frequency of GJB2, GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India.

Genetically caused nonsyndromic hearing loss is highly heterogeneous. Inspite of this large heterogeneity, mutations in the genes GJB2, GJB6 and SLC26A4 are major contributors. The mutation spectrum of these genes varies among different ethnic groups. Only a handful of studies focused on the altered genetic signature of these genes in different demographic regions of India but never focused on the eastern part of the country. Our study for the first time aimed to characterize the mutation profile of these genes in hearing loss patients of West Bengal state, India. Mutations in GJB2, GJB6 and SLC26A4 genes were screened by bidirectional sequencing from 215 congenital nonsyndromic hearing loss patients. Radiological diagnosis was performed in patients with SLC26A4 mutations by temporal bone CT scan. The study revealed that 4.65% and 6.97% patients had monoallelic and biallelic GJB2 mutations respectively. Six mutations were identified, p.W24X being the most frequent one accounting for 71.05% of the mutated alleles. Mutations in GJB6 including the previously identified deletion mutation (GJB6-D13S1830) were not identified in our study. Further, no patients harbored biallelic mutations in the SLC26A4 gene or the common inner ear malformation Enlarged Vestibular Aqueduct (EVA). The mutation profile of GJB2 in our study is distinct from other parts of India, suggesting that the mutation spectrum of this gene varies with ethnicity and geographical origin. The absence of GJB6 mutations and low frequency of SLC26A4 mutations suggest that additional genetic factors may also contribute to this disease.

Polymorphisms in CaSR and CLDN14 Genes Associated with Increased Risk of Kidney Stone Disease in Patients from the Eastern Part of India.

Kidney stone disease (KSD) is a major clinical problem imposing a large burden for both healthcare and economy globally. In India, the prevalence of kidney stone disease is rapidly increasing. This study aimed to evaluate the association between genetic defects in vitamin D receptor (VDR), calcium sensing receptor (CaSR) and claudin 14 (CLDN14) genes and kidney stone disease in patients from eastern India. We enrolled 200 consecutive kidney stone patients (age 18-60 years) (cases) and their corresponding sex and age matched 200 normal individuals (controls). To identify genetic variants responsible for KSD, we performed sequence analysis of VDR, CaSR and CLDN14 genes. Four non-synonymous (rs1801725, rs1042636, rs1801726 and rs2228570), one synonymous (rs219780) and three intronic single nucleotide polymorphisms (SNPs) (rs731236, rs219777 and rs219778) were identified. Genotype and allele frequency analysis of these SNPs revealed that, rs1801725 (Ala986Ser), rs1042636 (Arg990Gly) of CaSR gene and rs219778, rs219780 (Thr229Thr) of CLDN14 gene were significantly associated with KSD. Serum calcium levels were significantly higher in subjects carrying 986Ser allele and calcium excretion was higher in subjects bearing 990Gly allele. In conclusion, rs1801725, rs1042636, rs219778 and rs219780 SNPs were associated with kidney stone risk in patients from the eastern part of India.

Functional analysis of thyroid peroxidase gene mutations detected in patients with thyroid dyshormonogenesis.

Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones. We aimed to identify the spectrum of mutations in the TPO gene leading to hypothyroidism in the population of West Bengal to establish the genetic etiology of the disease. 200 hypothyroid patients (case) and their corresponding sex and age matched 200 normal individuals (control) were screened depending on their clinical manifestations. Genomic DNA was isolated from peripheral blood samples and TPO gene (Exon 7 to Exon 14) was amplified by PCR. The PCR products were subjected to sequencing to identify mutations. Single nucleotide changes such as Glu 641 Lys, Asp 668 Asn, Thr 725 Pro, Asp 620 Asn, Ser 398 Thr, and Ala 373 Ser were found. Changes in the TPO were assayed in vitro to compare mutant and wild-type activities. Five mutants were enzymatically inactive in the guaiacol and iodide assays. This is a strong indication that the mutations are present at crucial positions of the TPO gene, resulting in inactivated TPO. The results of this study may help to develop a genetic screening protocol for goiter and hypothyroidism in the population of West Bengal.

Role of peroxisome proliferator-activated receptor gamma gene polymorphisms in type 2 diabetes mellitus patients of West Bengal, India.

AIMS/INTRODUCTION: Peroxisome proliferator activated receptor gamma (PPARG) is a nuclear hormone receptor of the ligand-dependent transcription factor involved in adipogenesis, and a molecular target of the insulin sensitizer, thiazolidinediones. The present study aimed to investigate whether the PPARG gene is associated with type 2 diabetes mellitus and its related traits within the population of West Bengal, India. MATERIALS AND METHODS: The study participants (200 type 2 diabetes mellitus and 200 normal individuals) were chosen randomly, and the variants were screened by direct sequencing. RESULTS: The results showed that rs1801282 (odds ratio 0.66; 95% confidence interval 0.15-2.96; P = 0.57) and rs3856806 (odds ratio 1.23; 95% confidence interval 0.73-2.06; P = 0.44) variants of the PPARG gene were not associated with type 2 diabetes mellitus. CONCLUSIONS: The results showed that the PPARG gene was not associated with type 2 diabetes mellitus in our study population. As the lack of association might come from the small sample size, further studies with larger sample size are required to verify the present observation.

Genetic analysis of thyroid peroxidase (TPO) gene in patients whose hypothyroidism was found in adulthood in West Bengal, India.

Recent research has revealed that genetic defects due to mutation in the Thyroid Peroxidase (TPO ) gene can lead to thyroid dysfunction in the population. We aimed to study the association between genetic defects in TPO gene and patients with hypothyroidism found in adult age. Two hundred consecutive treatment naive hypothyroid patients (age ≥ 18 years) (cases) who were negative for anti TPO antibody and their corresponding sex and age matched two hundred normal individuals (controls) were enrolled. The 17 exonic regions of the TPO gene were amplified and sequenced directly. We identified 6 different previously known single nucleotide polymorphisms (SNPs) and 2 novel deletions in TPO gene. Two of the six SNPs revealed a significant association with hypothyroidism; Thr725Pro (rs732609) and Asp666Asp (rs1126797). The c.2173C allele of the Thr725Pro in TPO showed a significant association among hypothyroid patients compared to controls (p = 0.01; Odds ratio=1.45; 95% CI: 1.09-1.92) suggesting it to be a potential risk allele toward disease predisposition. Analysis of genotype frequencies of the polymorphism between the two groups demonstrated CC as a potential risk genotype (p = 0.006; Odds ratio=1.95; 95% CI: 1.2-3.15) for the disease while another SNP Asp666Asp (c.1998T allele) showed protectiveness towards the disease (p = 0.006; Odds ratio = 0.67; 95%CI: 0.50-0.89). To our knowledge, this is first study reporting the role of TPO gene with hypothyroidism in a population of Asian Indian origin. The study threw up the possibility of TPO gene polymorphisms as a possible pathogenetic mechanism of hypothyroidism.