Clinical and Angiographic Profiles of Myocardial Infarction in a Young South Indian Population.

Introduction Myocardial infarction (MI) in young South Indians presents a shifting epidemiological landscape, challenging traditional perceptions of cardiovascular diseases. This study investigates the clinical and angiographic profiles of MI in this subgroup of the population in detail, emphasizing the interaction between lifestyle, environmental, and genetic factors that contribute to the incidence of MI in younger people. Methodology Utilizing a descriptive observational design, the study analyzed data from 70 young adults (aged 18-45 years) admitted to Frontier Lifeline Hospital, Chennai, with acute MI over six months. Patient demographics, clinical characteristics, and angiographic findings were collected and analyzed using standardized protocols. Statistical analysis employed chi-square tests and subgroup analyses to assess associations and differences between diabetic and non-diabetic patients. Results The study revealed a predominance of males (84.29%) among MI cases, with ST-elevation myocardial infarction (STEMI) being the most common presentation (52.86%). Anterior wall involvement was prevalent (50%), and left ventricular systolic dysfunction (LVSD) was observed in the majority (67%) of patients. Chest pain (87%) was the predominant symptom, and diabetes (47%) and hypertension (47%) were the risk variables that were most common. Angiographically, the left anterior descending artery (LAD) was often affected (51%), with single-vessel disease predominating (41.43%). Conclusion The findings underscore the significance of early detection and intervention strategies for MI in young South Indians. Gender-specific risk assessment, prompt diagnosis, and tailored treatment approaches are imperative. The high prevalence of LVSD highlights the burden of cardiac morbidity, particularly in diabetic individuals. Lifestyle modifications and weight management interventions are crucial for MI prevention. This study provides insights into the frequency and features of MI in young South Indians, emphasizing the importance of collaborative efforts for early identification and control of modifiable risk factors to mitigate the burden of coronary artery disease (CAD) in this population subset.

Ethnic Differences, Lung Cancer Risk, and Association of NRF2 Gene Polymorphism with Gemcitabine-Based Chemotherapy.

INTRODUCTION: The cancer burden is rising every year. Lung cancer is one of the most common cancers and non-small cell lung cancer is the most common type. Chemotherapy based on platinum drugs and third-generation nucleoside anti-metabolites such as gemcitabine are used widely. Gemcitabine has a complex metabolic pathway, with many mechanisms contributing to its cytotoxicity. Derangements in the metabolic pathway genes contribute to drug resistance and toxicity with this drug. Association studies including these genetic polymorphisms in the metabolic pathway, clinical outcomes, and cancer risk reported inter-individual differences. Thus, the aim of this study was to ascertain the role of these genetic variants in South Indian cancer patients treated with gemcitabine-based therapy. METHODS: The study was done with 184 healthy volunteers for frequency establishment and 123 cancer patients were treated with gemcitabine-based chemotherapy for response and toxicity assessment. The participants were aged 18-65 years and resided in the southern states of India. DNA extraction was done from the leukocyte fraction of the blood by phenol-chloroform extraction procedures and genotyping was done by reverse transcription-polymerase chain reaction (RT-PCR) techniques to identify DNA repair gene polymorphisms. Tumor response was determined using Response evaluation criteria in solid tumors (RECIST) guidelines and toxicity using Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. The patients were followed up for survival analysis. RESULTS: The minor allele frequency of the single nucleotide polymorphism (SNP) NRF2-617 C>A (rs6721961) in the healthy population was 12.8%. SNPs were in Hardy-Weinberg equilibrium (p>0.05). Gender-based differences were not observed with the studied SNP in the healthy population and the lung cancer patients. These frequencies of NRF2 were found to be similar when compared to EUR (European) and all the South Asian subpopulations. They are significantly divergent compared to AFR (African), AMR (American), and EAS (East Asian) populations. The minor allele frequency in cancer patients was found to be 14.2% and the lung cancer risk with the SNP studied could not be detected. There was no association found with the response, toxicity, and survival among lung cancer patients. CONCLUSION: NRF2, being a multifaced molecule, did not show a significant association with lung cancer risk, response, and toxicity in patients with gemcitabine-based chemotherapy.

Impact of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions in individuals living with epilepsy: a case-control study.

Epilepsy is characterized by repeated seizure activity. Valproate, a commonly used antiepileptic drug, shows large inter-individual variation in plasma valproic levels and causes many adverse drug reactions. Aim: To find the influence of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions and plasma valproic acid levels in people with epilepsy. Methods: We recruited 158 people with epilepsy (79 cases and 79 controls) from an epilepsy clinic. Steady-state plasma valproic acid levels were measured using liquid chromatography-mass spectrometry and genotyping of CYP2C9 variants was carried out with helps of RT-PCR. Results: The presence of a mutant heterozygous genotype showed an odds ratio (OR) of 2.82 (95% CI: 1.10-7.24) and the adjusted OR was 5.39 (95% CI: 1.69-17.16). There was no significant difference in steady-state plasma valproate concentration between genotypes. Conclusion: The presence of a mutant heterozygous CYP2C9 genotype possesses five-times the risk of developing adverse drug reactions to valproate in people with epilepsy.

Hyperamylasemia is not Associated with Dipeptidyl Peptidase 4 Inhibitors in South Indian Adults with Type 2 Diabetes Mellitus.

Introduction: Although not definitive, there is small increased risk of acute pancreatitis with the use of dipeptidyl peptidase 4 inhibitors (DPP4i). Hence, there is an interest in the elevation of pancreatic enzymes among type 2 diabetes mellitus (T2DM) patients using DPP4i. However, the studies regarding their association are limited and provide conflicting results. Moreover, there are no such studies among South Indian T2DM patients. Hence, we evaluated the prevalence of hyperamylasemia among South Indian T2DM patients and its association with DPP4i use. Methods: This cross-sectional study was conducted at a tertiary health care center from South India. Adult T2DM patients on stable doses of antidiabetic medications for at least previous 3 months were included in the study. Patients with other types of diabetes mellitus, gall stones, diabetic ketoacidosis, acute illness, chronic kidney disease and untreated hypothyroidism were excluded from the study. All participants were evaluated with glycemic parameters, serum creatinine and serum amylase. Hyperamylasemia was defined as serum amylase ≥220 U/L. Results: A total of 200 participants were included in the study among whom 93 patients were not on DPP4i whereas 107 were on DPP4i including 41 (38.32%) each on teneligliptin and sitagliptin. Baseline characteristics including glycemic measures were comparable between DPP4i users and nonusers. A total of 14 patients (7%) had hyperamylasemia but the prevalence of hyperamylasemia did not differ between DPP4i users and nonuser (6/107 vs. 8/93, P = 0.42). Conclusions: Asymptomatic hyperamylasemia is not uncommon in South Indian T2DM patients but is not associated with the use of DPP4i.

Is there any difference in the development of mandibular third molars according to the type of impaction: An orthopantomographic study in south Indian children and adolescents.

Development of third molars and their influence on the dental arch is a major concern in clinical dentistry especially, orthodontics and oral surgery. Lately, their position, eruption potential and development has become a subject of interest in forensic practice. The present study was aimed to determine whether if there is any difference in the development of the mandibular third molars according to the impaction type. Orthopantomographs (n = 1112) from 478 males and 634 females between 15 and 22 years old were analysed. In each radiograph, impaction status and the developmental stage of mandibular third molars were determined. Descriptive statistics were performed at developmental stages D to H. For stage G, there was a delay by 0.74 and 0.62 years for mesioangular impaction, 0.89 and 0.33 years for horizontal impaction, 1.43 and 0.9 years for distoangular impaction and 1.74 and 1.1 years for vertical impaction, in males and females. For stage H, delay by 0.17 and 0.74 years, 0.05 and 0.06 years, 0.48 and 1.48 years and 0.62 and 0.62 years, respectively for all impaction variants in both sexes. Mean chronological age of the distoangular and vertically impacted mandibular third molars were higher in certain developmental stages than mesioangular and horizontal impactions. Our findings concluded that distoangular and vertical impaction variants mineralize more slowly than mesioangular and horizontal variants, however these differences were smaller. Therefore, no distinction is required between impaction types for dental age estimation especially in the prediction of the age of majority (18 years).

Frequency and association of self-reported oral cancer among individuals with type 2 diabetes at a tertiary care diabetes centre in South India - A retrospective study.

AIM: To assess the frequency of self-reported oral cancer and associated factors among individuals with type 2 diabetes (T2D) at a tertiary care diabetes centre in South India. METHODS: Individuals with T2D who reported that they had oral cancer were included from the Diabetes Electronic Medical Records (DEMR) database. To assess the association of oral cancer with T2D, a retrospective nested case-control study design was adopted. Individuals with T2D and oral cancer diagnosed after the diagnosis of T2D (n = 78) were considered 'cases', while T2D without oral cancer were considered 'controls' (312) [in a ratio of 1:4 for cases and controls]. The cases and controls were matched for age, gender and duration of diabetes. Logistic regression was used to model predictors of oral cancer in T2D patients. RESULTS: Oral cancer was reported in 78 out of 379,138 (0.02%) individuals with T2D registered at the centre. Logistic regression analysis showed that a HbA1c value ≥ 9% had a significant association with oral cancer with an odds ratio of 2.3 (95% CI: 1.2-4.6) after adjusting for confounding factors. Among individuals with T2D, higher frequency of oral cancer prevalence and risk was observed among those who used any form of tobacco (32.6%, OR = 2.52, 95% CI: 1.5-4.3), consumed alcohol (29.2%, OR = 2.01, 95% CI: 1.2-3.3), and those with hypertension (23.9%, OR = 2.05, 95% CI: 1.2-3.6) and hypertriglyceridemia (24.7%, OR = 1.66, 95% CI: 1.01-2.7). Significant independent predictors of oral cancer among T2D were tobacco use (OR = 2.06, 95% CI: 1.1-4.00), high HbA1c (OR = 1.3, 95% CI: 1.03-1.5), hypertension (OR = 2.3, 95% CI: 1.3-4.2) and insulin use (OR = 1.8, 95% CI: 1.03-3.2). CONCLUSIONS: Regular dental check-ups as part of the follow-up for individuals with T2D will identify and diagnose oral cancer earlier. Further research is required to assess the physiological and biological mechanisms leading to oral cancer in individuals with T2D.

Targeted exome sequencing in South Indian patients with Familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD). OBJECTIVES: In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing. METHODS: 54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC). Targeted exome sequencing was performed using 23 gene panel associated with lipid metabolism. RESULTS: All subjects showed the presence of family history of CAD, 38(70%) patients had corneal arcus whereas only 06(11%) subjects had xanthomas. As per the DLCNC, definite, probable, possible and unlikely FH were 48%, 30%, 11% and 11% respectively. Mutations were observed in 12 of the 23 gene panel with CETP, APOA5, EPHX2 and SREBP2 genes were identified for the first time in Indian FH patients. All 19 mutations including a novel frame-shift mutation in LDLR gene were reported for the first time in Indian FH patients. These mutations were identified in 28(52%) subjects and interestingly ∼73% of the clinically identified FH patients didn't harbour mutations in FH classical genes (LDLR, ApoB, PCSK9). CONCLUSION: This is the first study in the South Indian FH patients to perform targeted exome sequencing. Absence of mutations in the FH classical genes strongly indicates the polygenic nature of FH, further underscoring the importance of targeted exome sequencing for identifying mutations in genetically diverse Indian population.

Legal age determined by a new threshold value of third molar maturity index in subjects with impacted mandibular third molars: An orthopantomographic study in south Indian adolescents.

Third molars are one of the few biological markers available for age estimation in juveniles, especially for the estimation of the 18-year-age threshold. Literature has indicated that impaction has an influence on the development of third molars, which could possibly result in age misclassifications. The present study is intended to identify an alternative cut-off value of the third molar maturity index (I3M) in impacted mandibular third molars and also to evaluate its applicability in estimating the major (≥ 18 years)/minor (< 18 years) status. A total of 1330 digital orthopantomograms (OPGs) of 665 male and 665 female south Indian adolescents aged from 15 to 22 years were collected and assessed. Eight hundred forty OPGs (63.1%) represented test sample, and 490 OPGs (36.9%) represented validation sample. I3M was measured for the total sample. Logistic regression, receiver operating characteristic (ROC) curve analysis, and Youden's index were used to test the performance of the method in the test sample. An alternative cut-off value of I3M < 0.17 was established for the highest value of the Youden's index of 0.598 for both sexes. When tested in validation sample, it has resulted in sensitivity and specificity values of 0.91 (95% CI; 0.86-0.95) and 0.90 (95% CI; 0.78-0.91) in males and 0.86 (95% CI; 0.80-0.92) and 0.90 (95% CI; 0.83-0.95) in females. In conclusion, cut-off value of I3M < 0.17 could accurately discriminate adults from minors with impacted mandibular third molars. However, more work is needed to be done among a more diverse sample to confirm these findings.

Evaluation of the effect of impaction on the mineralization of mandibular third molars and forensic age estimation in a sample of south Indian children.

Assessment of third molar mineralization is a basic forensic odontological method available for age estimation in children and adolescents. Due to their protracted development into the late adolescence, their development has become the subject of interest and acquired great forensic importance. It is clearly evident in the literature that impaction factor has an influence on the rate of maturation of the third molars. In this regard, the present study was undertaken to test the relationship between impaction and its concomitant effect on the mineralization of the third molar and forensic age estimation. A total of 520 digital orthopantomograms (OPG) of 260 males and 260 females of south Indian origin were assessed retrospectively. Maturation of the third molars (I3M) was assessed using the method of Cameriere et al. (Int J Leg Med 122 (6):493-497, 2008). Impaction status was determined according to the position of lower right and left third molars in relation to the long axis of the second molars. Out of the total sample, 68.1% of lower left third molars and 71.2% of lower right molars were impacted. Statistical measures for I3M were calculated in the males and females for both impacted and non-impacted third molars. It was ascertained that the mean age and I3M values were higher in impacted third molars, indicating the slower rate of maturation than non-impacted ones. The sensitivity and specificity of the test (I3M < 0.08) was 96.2% and 72.4% for non-impacted third molars and 46.2% and 87% for impacted third molars, respectively. Our findings indicate that the cut-off value of I3M < 0.08 resulted in greater number of age misclassifications (false negatives) for impacted molars, highlighting the need for new cut-off value of I3M to meet the legal standards. It was concluded that the mineralization of impacted third molars was slower compared to non-impacted ones in south Indian males and females. Further studies are warranted to validate these findings among a larger and more diverse sample.

Prevalence of vitamin B12 deficiency in South Indians with different grades of glucose tolerance.

AIMS: To determine the prevalence of vitamin B12 deficiency in an urban south Indian population in individuals with different grades of glucose tolerance. METHODS: A total of 1500 individuals [900 normal glucose tolerance (NGT), 300 prediabetes and 300 type 2 diabetes (T2DM)] who were not on vitamin B12 supplementation were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES) follow-up study. Anthropometric, clinical and biochemical investigations, which included vitamin B12, insulin, homocysteine, HbA1c and serum lipids, were measured. Vitamin B12 ≤ 191 pg/ml was defined as absolute vitamin B12 deficiency and vitamin B12 > 191 pg/ml and ≤ 350 pg/ml as borderline deficiency. RESULTS: The mean levels of vitamin B12 significantly decreased with increasing degrees of glucose tolerance (NGT 444 ± 368; prediabetes 409 ± 246; T2DM 389 ± 211 pg/ml, p = 0.021). The prevalence of absolute vitamin B12 deficiency was 14.9% while 37.6% had borderline deficiency. The prevalence of absolute vitamin B12 deficiency was significantly higher among individuals with T2DM (18.7%) followed by prediabetes (15%) and NGT(13.7%) [p for trend = 0.05]. The prevalence of vitamin B12 significantly increased with age (p < 0.05) and in those with abdominal obesity (p < 0.001). Men and vegetarians had twice the risk of vitamin B12 deficiency compared to women and non-vegetarians, respectively. Among individuals with NGT, prediabetes and T2DM, vitamin B12 negatively correlated with homocysteine. CONCLUSION: This study reports that the levels of vitamin B12 decreased with increasing severity of glucose tolerance.

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population.

This study reports on the association of genetic variants selected from previous genome-wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30-2.30, P = 1.72 × 10-4 ) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.

Dietary fat intake and its association with risk of selected components of the metabolic syndrome among rural South Indians.

CONTEXT: There is limited literature on the dietary fat intake of rural Indian populations, particularly in relation to the risk of metabolic syndrome (MS). AIM: This study aims to assess the dietary fat intake and analyze its association with the risk of selected components of the MS among rural population in the state of Tamil Nadu. SETTINGS AND DESIGN: Adults (n = 27012) ≥20 years of age were recruited from the rural component of the Chennai Urban Rural Epidemiological Study, a cross-sectional study conducted in 42 villages in Kanchipuram District of Tamil Nadu. SUBJECTS AND METHODS: Using a validated food frequency questionnaire, data were obtained on the fat intake among 6907 adults. Anthropometric and clinical measures were collected using standard methods. The components of the MS assessed were abdominal obesity, hypertension, and impaired fasting glucose. All analyses were performed using SPSS software (version 20). RESULTS: Prevalence of abdominal obesity, hypertension, and impaired fasting glucose were significantly higher in the highest quintile of fat intake (33%, P < 0.001; 39%, P = 0.04, and 23.3%, P = 0.003, respectively). Highest intake of fat was also significantly associated with risk of abdominal obesity (P < 0.001), hypertension (P = 0.04), and impaired fasting glucose (P = 0.01). Sunflower oil as the main cooking oil was significantly associated with a higher risk of these components of the MS (P for trend <0.001) compared to traditional oils and palmolein. CONCLUSIONS: Higher dietary fat was significantly associated with risk of components of the MS and use of sunflower oil as main cooking oil increased metabolic risk in rural South Indians.

Influence of dihydrofolate reductase gene polymorphisms rs408626 (-317A>G) and rs442767 (-680C>A) on the outcome of methotrexate-based maintenance therapy in South Indian patients with acute lymphoblastic leukemia.

PURPOSE: The most common cause of treatment failure in acute lymphoblastic leukaemia (ALL) is the relapse. Genetic polymorphisms of dihydrofolate reductase (DHFR) enzyme affect the response to methotrexate (MTX) treatment. Inter-individual variability exists in the distribution of DHFR variants, and they influence MTX treatment outcome. To the best of our knowledge, there are no genetic studies reported from India, which have explored the influence of DHFR variants on the outcome of MTX treatment. Therefore, we aim to study the influence of DHFR rs408626 (-317A>G) and rs442767 (-680C>A) variants on ALL outcome in South Indian patients. METHODS: A total of 70 ALL patients who were on MTX-based maintenance therapy were recruited for the study. DNA was extracted from leukocytes, and genotyping was done by real-time PCR. RESULTS: The DHFR-317GG genotype was associated with the increased risk of relapse in patients with ALL (relative risk 2.25, 95% confidence interval (CI) 1.38 to 3.6, p = 0.02). DHFR-317AA and -680CA genotypes were found to be associated with severe leucopenia (p < 0.05). In Cox regression model, -317GG genotype was found to have lower relapse-free survival (hazard ratio (HR) 2.56, 95% CI 1.06 to 6.19, p = 0.03) and overall survival (HR 3.72, 95% CI 1.44 to 9.65, p = 0.007). Similarly, patients with white blood cell (WBC) count >50,000 cells/mm(3) were also found to have lower relapse-free survival (HR 2.20, 95% CI 1.10 to 4.79, p = 0.04) and overall survival (HR 3.30, 95% CI 1.45 to 7.53, p = 0.004). CONCLUSION: The GG genotype of DHFR-317A>G variant is associated with increased risk of ALL relapse and lower overall survival in South Indian population. Both variants of DHFR (-317 AA and -680 CA) are found to be associated with severe leucopenia caused by MTX.

Association of TCF7L2 Polymorphism with Diabetic Nephropathy in the South Indian Population.

The transcription factor 7-like 2 (TCF7L2) gene plays a significant role in the development of type 2 diabetes and diabetic nephropathy. The aim of this study was to investigate the association of TCF7L2 rs12255372 (G/T)polymorphism with type 2 diabetic nephropathy in the South Indian population. A total of 2102 subjects, 927 normal glucose tolerant (NGT) subjects, 598 type 2 diabetic subjects without nephropathy (DM), and 577 type 2 diabetic subjects with nephropathy (DN) were genotyped by MassARRAY. As compared to the NGT group, the odds ratio (adjusted for age, sex, BMI, HbA1c, and systolic BP) computed for the GT/TT genotype taking the GG genotype as reference was found to be 2.02 (95% CI: 1.16-3.51, p = 0.013) for DN and 1.94 (95% CI: 1.36-2.78, p = 0.0002) for DM. The genotype frequency was not significantly different between the DM and DN groups. In conclusion, the rs12255372 polymorphism in the TCF7L2 gene is associated with type 2 diabetes and DN but its association with DN is mediated through diabetes.

Accuracy of four dental age estimation methods in southern Indian children.

INTRODUCTION: For various forensic investigations of both living and dead individuals, the knowledge of the actual age or date of birth of the subject is of utmost importance. In recent years, age estimation has gained importance for a variety of reasons, including identifying criminal and legal responsibility, and for many other social events such as birth certificate, marriage, beginning a job, joining the army and retirement. Developing teeth are used to assess maturity and estimate age in number of disciplines; however the accuracy of different methods has not been assessed systematically. The aim of this study was to determine the accuracy of four dental age estimation methods. MATERIALS AND METHODS: Digital Orthopantomographs (OPGS) of South Indian children between the ages of 6 and 16 y who visited the department of Department of Oral medicine and Radiology of GITAM Dental College, Visakhapatnam, Andhra Pradesh, India with similar ethnic origin were assessed. Dental age was calculated using Demirjian, Willems, Nolla, and adopted Haavikko methods and the difference between estimated dental age and chronological age were compared with paired t-test and Wilcoxon signed rank test. RESULTS: An overestimation of the dental age was observed by using Demirjian and Nolla methods (0.1±1.63, 0.47±0.83 years in total sample respectively) and an underestimation of dental age was observed by using Willems and Haavikko methods (-0.4±1.53, -2.9±1.41 years respectively in total sample). CONCLUSION: Nolla's method was more accurate in estimating dental age compared to other methods. Moreover, all the four methods were found to be reliable in estimating age of individuals of unknown chronological age in South Indian children.

Accuracy of Demirjian's 8 teeth method for age prediction in South Indian children: A comparative study.

INTRODUCTION: Demirjian's method of tooth development is most commonly used to assess age in individuals with emerging teeth. However, its application on numerous populations has resulted in wide variations in age estimates and consequent suggestions for the method's adaptation to the local sample. Original Demirjian's method utilized seven mandibular teeth, to which recently third molar is added so that the method can be applied on a wider age group. Furthermore, the revised method developed regression formulas for assessing age. In Indians, as these formulas resulted in underestimation, India-specific regression formulas were developed recently. The purpose of this cross-sectional study was to evaluate the accuracy and applicability of original regression formulas (Chaillet and Demirjian 2004) and India-specific regression formulas (Acharya 2010) using Demirjian's 8 teeth method in South Indian children of age groups 9-20 years. METHODS: The present study consisted of 660 randomly selected subjects (330 males and 330 females) were in the aged ranging from 9 to 20 years divided into 11 groups according to their age. Demirjian's 8 teeth method was used for staging of teeth. RESULTS: Demirjian's method underestimated the dental age (DA) by 1.66 years for boys and 1.55 years for girls and 1.61 years in total. Acharya's method over estimated DA by 0.21 years for boys and 0.85 years for girls and 0.53 years in total. The absolute accuracy was better for Acharya's method compared with Demirjian method. CONCLUSION: This study concluded that both the Demirjian and Indian regression formulas were reliable in assessing age making Demirjian's 8 teeth method applicable for South Indians.

Association of serum adiponectin with diabetic microvascular complications among south Indian type 2 diabetic subjects - (CURES-133).

OBJECTIVES: To assess the association of serum adiponectin and microvascular complications of diabetes in an urban south Indian type 2 diabetic population. DESIGN AND METHODS: Diabetic subjects [n=487] were included from Chennai Urban Rural Epidemiology Study (CURES). Four-field stereo retinal color photography was done and diabetic retinopathy (DR) was classified as non-proliferative DR (NPDR) or proliferative DR (PDR) according to the Early Treatment Diabetic Retinopathy Study grading system. Sight threatening DR (STDR) was defined as the presence of NPDR with diabetic macular edema, and/or PDR. Neuropathy was diagnosed if vibratory perception threshold of the great toe using biothesiometry exceeded ≥20V. Nephropathy was diagnosed if urinary albumin excretion (UAE) was ≥30µg/mg creatinine. Serum total adiponectin levels were measured by radioimmunoassay. RESULTS: Subjects with any microvascular complications had significantly higher levels of adiponectin levels compared to those without the complications (geometric mean: 6.1 vs. 5.3µg/mL, p=0.004). The adiponectin level was significantly higher in subjects with DR (6.8 vs. 5.5µg/mL, p=0.004) and neuropathy (5.6 vs. 6.5µg/mL, p=0.024) compared to those without. Adiponectin levels were not significantly different in subjects with and without nephropathy. Serum adiponectin levels increased with the severity of DR [No DR - 5.5µg/mL; NPDR without DME - 6.5µg/mL; STDR - 8.3µg/mL, p=0.001]. Regression analysis revealed adiponectin to be associated with microvascular disease (presence of neuropathy and/or retinopathy and/or nephropathy) (OR: 1.44, 95% CI: 1.01-2.06, p=0.049) even after adjusting for age, gender, BMI, HbA1c, diabetes of duration, serum cholesterol and triglycerides, hypertension and medication status. CONCLUSION: In Asian Indians with type 2 diabetes, serum adiponectin levels are associated with microvascular complications and also with the severity of retinopathy.

Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients.

Metformin is an oral antidiabetic drug, commonly used for treating type 2 diabetes mellitus (T2DM) patients. It is transported into the hepatocytes by polyspecific organic cation transporter 1, which is encoded by the gene SLC22A1. It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Previous studies have demonstrated this in other populations with conflicting results, but it remains to be elucidated in Indian population. Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. A total of 122 newly detected, treatment naive T2DM patients of either sex were included in this study. The patients were started on metformin monotherapy and followed up for 12 weeks. Genotype was determined using qRT-PCR. Before and after treatment with metformin, body mass index (BMI), serum lipid profile, glycated hemoglobin (HbA1c), fasting and postprandial glucose level, and blood pressure (BP) were measured. The study cohort mean age was 49.57 ± 9.88 years. Of the 122 T2DM patients, 93 were classified as responders and 29 as non-responders based on fall in HbA1c levels. Interestingly, carriers of one variant allele 'C' (AC) of rs622342 polymorphism were less among the responders than those who did not (44.8 vs. 22.6 %). The response was even lesser (13.8 vs. 4.3 %) in carriers of two copies of "C" allele (CC). On the contrary, patients with two copies of allele 'A' (AA) had 5.6 times greater chance of responding to metformin treatment. A similar trend was observed when the proportion was analyzed under different genetic models (OR 3.85, 95 % CI 1.61-9.19 for dominant; OR 3.56, 95 % CI 0.83-15.26 for recessive; OR 0.35, 95 % CI 0.14-0.86 for over-dominant; and OR 4.10, 95 % CI 1.78-9.43 for additive). Further, metformin showed significant beneficial effects on BMI, HbA1c, FPG, PPG, lipid parameters and BP. These data suggest that the allele and genotypes of SLC22A1 rs622342 gene polymorphism were associated with the therapeutic efficacy of metformin in South Indian patients with T2DM.

Drug-induced gingival overgrowth: the genetic dimension.

BACKGROUND: Currently, the etiology of drug-induced gingival overgrowth is not entirely understood but is clearly multifactorial. Phenytoin, one of the common drugs implicated in gingival enlargement, is metabolized mainly by cytochrome P450 (CYP)2C9 and partly by CYP2C19. The CYP2C9 and CYP2C19 genes are polymorphically expressed and most of the variants result in decreased metabolism of the respective substrates. AIMS: The present study was undertaken to investigate the influence of the CYP2C9*2 and *3 variant genotypes on phenytoin hydroxylation in subjects diagnosed with epilepsy from South India, thus establishing the genetic polymorphisms leading to its defective hydroxylation process. MATERIALS AND METHODS: Fifteen epileptic subjects, age 9 to 60 years were included in the study. Among the study subjects, 8 were males and 7 were females. Genomic DNA was extracted from patients' blood using Phenol-chloroform method and genotyping was done for CYP2C9 using customized TaqMan genotyping assays on a real time thermocycler, by allelic discrimination method. The genetic polymorphisms *1, *2 and *3 on CYP2C9 were selected based on their function and respective allele frequencies in Asian subcontinent among the Asian populations. RESULTS: CYP2C9*1*2 and CYP2C9*3/*3 were identified with equal frequency in the study population. There were seven subjects with CYP2C9*1/*2 genotype (heterozygous mutant), one subject with CYP2C9*1/*1 (wild type) and seven study subjects with CYP2C9*3/*3 (homozygous mutant). CONCLUSION: The results obtained in the present study will be helpful in the medical prescription purposes of phenytoin, and a more personalized patient approach with its administration can be advocated.

Genotype, allele and haplotype frequencies of four TCL1A gene polymorphisms associated with musculoskeletal toxicity in the South Indian descent.

INTRODUCTION: Decline in circulating estrogen levels causes lessening of bone mass accompanied with musculoskeletal pain, which is the primary cause of treatment discontinuation in patients taking aromatase inhibitors. Evidence from recent genome-wide association studies (GWAS) suggests that the genetic variability underlying TCL1A gene increases the risk of aromatase inhibitors (AIs) - induced musculoskeletal toxicity. Currently, no data is available on the frequency distribution of TCL1A gene polymorphisms in Indians. METHODS: In this pilot study, we used TaqMan fluorescent probes to assess the genotypes of four TCL1A gene polymorphisms associated with musculoskeletal toxicity in 247 healthy homogenous South Indian subjects on real time thermocycler. Haplotype estimation and pairwise linkage disequilibrium (LD) analysis were executed by Haploview. RESULTS: The incidence of polymorphic variant allele (G) frequencies of rs7158782, rs7159713, rs2369049 and rs11849538 were 22.1%, 23.5%, 18.2% and 22.9% in the study population, respectively. The polymorphisms were found to be in complete LD with each other. Four different haplotypes, each of which having a frequency of above 1% were inferred in South Indians using an expectation-maximization algorithm. Notably, three haplotypes were found to be population specific viz H4 A-A-A-G (1.2%) for South India, H5 G-G-A-C (1.3%) for JPT and H6 G-G-G-C (40.4%) for YRI. Further, H3 G-G-A-G (2.3-16.3%) haplotype occurs primarily in Asians and is virtually absent in Africans. Overall, the genetic variability and haplotype profile of South Indian population revealed significant inter-racial variability compared with HapMap data. CONCLUSION: This documentation contributes for further investigations on the pharmacogenetics of AIs in South Indians.