Current Scenario and Future Prospects of Adverse Drug Reactions (ADRs) Monitoring and Reporting Mechanisms in the Rural Areas of India.

BACKGROUND: Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding, and prevention of adverse effects associated with drugs. The objective of PV is to ensure the safety of the medicines and patients by monitoring and reporting all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2- 24% of hospitalization cases are due to ADRs, of which 3.7% of patients have lethal ADRs. The reasons include the number of prescribed drugs, an increased number of new medicines in the market, an inadequate PV system for ADR monitoring, and a need for more awareness and knowledge about ADR reporting. Severe ADRs lead to enhanced hospital stays, increased treatment costs, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is essential to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1%, whereas worldwide, it is 5% due to a need for more awareness about PV and ADR monitoring among healthcare providers and patients. The main objective of this review is to highlight the current scenario and possible futuristic ways of ADR reporting methods in rural areas of India. We have searched the literature using PubMed, Google scholar, Indian citation index to retrieve the resources related to ADR monitoring and reporting in India's urban and rural areas. Spontaneous reporting is the most commonly used PV method to report ADRs in India's urban and rural areas. Evidence revealed that no effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR, thus increasing the threat to the rural population. Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring, and reporting of ADRs in rural areas.

Comparison of Clonidine with Bupivaicaine vs Plain Bupivaicaine in Transversus Abdominis Plane (TAP) Block in Women Undergoing Cesarean Delivery Under Spinal Anesthesia: Randomized Clinical Trial.

Introduction: Transversus abdominis plane (TAP) block is a technique of regional anesthesia, introduced by Rafi in 2001. Various additives have been added to prolong the duration of effect of TAP block. We conducted this study to see if addition of clonidine to bupivacaine significantly increases the duration of effect of TAP block. Materials and Methods: This randomized, parallel group, placebo controlled double blind clinical trial was conducted on 100 healthy participants (ASAII) undergoing LSCS under Spinal anesthesia (SA) from Jan 2021 to July 2021 after consent of Institutional Ethics Committee. Women with contraindications to spinal anesthesia, allergy to any of the drugs or not-suitable for cesarean under SA were excluded. After written informed consent, eligible participants were randomly allocated into two groups using computer generated random number tables using serially numbered opaque sealed envelopes. 48 out of 50 participants in group A (Bupivacaine) were given TAP block with 20 ml of 0.25% bupivacaine bilaterally. 2 women were excluded because of conversion to General Anesthesia. Similarly, 47 out of 50 participants in Group B (Bupivacaine + Clonidine) were given TAP block with 20 ml of 0.25% bupivacaine plus 1.0 mcg/kg clonidine bilaterally after completion of surgery using 18 G Tuohy needle. Separate person used to fill the drugs for block. Participants were assessed for duration of analgesic effect of TAP block measured as the time to request for additional analgesia. Additional analgesic requirement was noted. Participants were assessed for side effects of clonidine like hypotension, bradycardia, sedation and dryness of mouth. Overall patient satisfaction was also noted. Data was analysed using Graphpad Prism 9, using Student's t-test for primary outcome and Mann-Whitney U test for secondary outcomes. Results: The mean 'duration of analgesic effect with TAP block' was 6.34 (SD1.26) hrs for 'Bupivacaine' group and 10.56 (SD2.12) hrs for 'Bupivacaine + Clonidine' group. None of the patients developed hypotension or bradycardia. 25% participants in Bupivacaine only group and 40.42% in Bupivacaine + Clonidine group were sedated (P < 0.05). 20.8% in 'Bupivacaine' group and 51.06% in 'Bupivacaine + Clonidine' group had dryness of mouth (P < 0.001). Patient satisfaction was equal in both the groups. Conclusion: Addition of clonidine to bupivacaine in the dose of 1 mcg/kg significantly increases the duration of analgesic effect of TAP block, decreases analgesic usage without significant increase in side effects.

Phytochemical profiling and biological activities of Diplazium esculentum (Retz.) Sw.: an edible vegetable fern.

OBJECTIVES: Diplazium esculentum (Retz.) Sw. is an edible vegetable fern of the Himalayan region with high nutritional and therapeutic value owing to its richness in various secondary metabolites and both macro and micronutrients. CONTENT: This updated review discusses the general traditional use, ethnopharmacology, phytochemistry, nutritional value, pharmacology, and toxicity concerns of D. esculentum. SUMMARY: The plant parts, viz. rhizomes, shoots, fronds and leaves, have immense ethnomedicinal importance, being traditionally used to cure several health disorders. Among other pharmacological effects, this botanical reveals excellent anti-inflammatory, analgesic, antifungal, antibacterial, antioxidant, anti-leishmanial, antioxidant, anaphylactic, antipyretic, anthelmintic and hepatoprotective activities, directly attributed to the presence of many secondary metabolites. From a pharmacological point of view, the excellent antioxidant potential of D. esculentum suggests its promising use for nutraceutical or functional food formulation purposes. OUTLOOK: Considering the evidences on popular ethnomedicinal uses of D. esculentum as an edible vegetable, its immense bio-potential, and multiple pharmacological roles, there is a huge need to evaluate its therapeutic applications in light of standard clinical trials.

The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions.

Introduction: Endometrial cancer is a hormone-dependent malignancy, and sex steroid hormones play a crucial role in its pathogenesis. Recent studies have demonstrated that microRNAs (miRNAs) can regulate the expression of sex steroid hormone receptors and modulate hormone signaling pathways. Our aim is to provide an overview of the current understanding of the role of miRNAs in endometrial cancer regulated by sex steroid hormone pathways. Methods: A thorough literature search was carried out in the PubMed database. The articles published from 2018 to the present were included. Keywords related to miRNAs, endometrial cancer, and sex steroid hormones were used in the search. Results: Dysregulation of miRNAs has been linked to abnormal sex steroid hormone signaling and the development of endometrial cancer. Various miRNAs have been identified as modulators of estrogen and progesterone receptor expression, and the miRNA expression profile has been shown to be a predictor of response to hormone therapy. Additionally, specific miRNAs have been implicated in the regulation of genes involved in hormone-related signaling pathways, such as the PI3K/Akt/mTOR and MAPK/ERK pathways. Conclusion: The regulation of sex steroid hormones by miRNAs is a promising area of research in endometrial cancer. Future studies should focus on elucidating the functional roles of specific miRNAs in sex steroid hormone signaling and identifying novel miRNA targets for hormone therapy in endometrial cancer management.

Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D) Polymorphism as a Conjoint Regulator of Coagulation, Fibrinolytic, and RAAS Pathway in Infertility and Associated Pregnancy Complications.

Despite the increase in assisted reproductive technologies, the high rates of infertility and pregnancy complications are a major concern to infertility specialists worldwide. Infertility may be attributed to pregnancy complications like thrombophilia, preeclampsia and fibrin-induced recurrent pregnancy loss (RPL). Renin-angiotensin-aldosterone system (RAAS) directly or indirectly causes preeclampsia and thrombophilia through the fibrinolytic pathway that ultimately leads to RPL or infertility. The underlying mechanisms of this interaction are still unclear. The present comprehensive review is intended to demonstrate the role and interaction of RAAS and fibrinolytic pathways in pregnancy complications. How this interaction can induce pregnancy complications, and ultimately infertility, is also discussed in the light of current evidence. This study also presents common markers that link RAAS and fibrinolytic processes in developing thrombophilia, preeclampsia and RPL. The common link in these pathways is ACE gene I/D polymorphism. Apart from ACE, PAI-1, VIIa, XIIa, AT1R, AT1AA, and TF are common molecules that can delineate the underlying causes of pregnancy complications and infertility.

10-degree reverse Trendelenburg position on hemodynamic parameters and block characteristics in unilateral spinal anesthesia in below knee orthopedic surgeries - can head up position do the trick?

Unilateral spinal anesthesia (USpA) is a technique used to restrict the effect of the spinal block on the operative side. 10-15 degrees reverse Trendelenburg position has been used to control the height of the spinal block using hyperbaric drugs. We aimed to study the effect of the 10-degree reverse Trendelenburg position on the quality of block and hemodynamic stability in unilateral spinal anesthesia in this hospital-based, double-blind, randomized clinical trial. 60 patients of both sexes between 20-60 years of age, undergoing below-knee orthopedic surgeries, were randomized into 2 groups. In both groups, spinal anesthesia was given with 2 mL bupivacaine heavy (0.5%), and the lateral position was maintained for 10 mins. Group 2 patients were kept in a 10-degree reverse Trendelenburg position throughout the surgery. The hemodynamic parameters and block characteristics of the two groups were compared using Epi Info statistical software. The onset of sensory block was faster in Group 1 (recumbent) compared to Group 2 (reverse Trendelenburg). The two-segment regression time was longer in the second group. In group 2, 73.3% of patients reached a level at T8 or below T8, compared to 46.7% in Group 1. The duration of sensory block and anesthesia was longer in Group 2. We conclude that reverse Trendelenburg of 10 degrees immediately after spinal anesthesia significantly limits the level of sensory block and prolongs the duration of unilateral spinal anesthesia.

Incidence and Risk Factors of "Postdural Puncture Headache" in Women Undergoing Cesarean Delivery under Spinal Anesthesia with 26G Quincke Spinal Needle, Experience of Medical College in Rural Settings in India 2019: A Prospective Cohort Study Design.

Introduction: Almost every cesarean delivery is done under spinal anesthesia because of ease of doing, rapid onset, avoids maternal and fetal risk of general anesthesia, promotes early recovery. Major complication especially in young women undergoing LSCS under spinal anesthesia is post dural puncture headache (PDPH) which is caused by cerebrospinal fluid leakage. There is wide variation in reported incidence of PDPH (0.3% to 40 %) after spinal anesthesia being affected by various procedure and non procedure related risk factors like age, gender, needle size and type, numbers of spinal attempts and previous history of PDPH. Methods: Prospective cohort study was conducted in 335 patients posted for caesarean section under spinal anesthesia from January 2019 to September 2019 in medical College situated in rural India. Spinal anesthesia was given by 26 G Quincke spinal needle. All patients were evaluated for incidence and severity of PDPH from post operative day 1 to day 5. Result: Incidence of PDPH was 11.4% in this study. Majority of patients (62.5%) were having mild pain. All patients reported PDPH with 72 hours. Conclusion: Body mass index (BMI), h/o PDPH, multiple attempts for successful spinal anesthesia did not have any significant association with PDPH in our study.

Investigating the Effect of the 10° Reverse Trendelenburg Position on Spinal Block Characteristics and Hemodynamic Parameters in Lower Limb Surgeries.

INTRODUCTION: The primary goal of spinal anesthesia in lower limb surgeries is to achieve a successful sensory and motor block. Adequate level of spinal block for lower limb orthopedic surgery is T10. Due to multiple factors affecting the level of spinal anesthesia, it is not always easy to control the level of spinal anesthesia.We proposed that maintaining patients in a 10° reverse Trendelenburg position after spinal anesthesia can significantly control the height of the sensory block, resulting in stable hemodynamics. MATERIALS AND METHODS: This study is a single centric, prospective, single-blinded randomized clinical trial (CTRI/2018/08/015455) conducted in a tertiary care center in Sub-Himalayan region in India from July 2018 to June 2019. Total 60 patients fulfilling our inclusion and exclusion criteria were recruited in the study and were divided into two groups. In the supine group, patients were positioned in the supine position, and in the Trendelenburg group, patients were positioned in a 10° reverse Trendelenburg position after administering spinal anesthesia with 12.5 mg bupivacaine heavy. The two groups were compared in terms of sensory block, motor block, and analgesia duration. Heart rate, blood pressure, mean arterial pressure, and hypotension were also compared between the two groups. RESULTS: Duration of sensory block, motor block, and analgesia were significantly higher in patients of the reverse Trendelenburg group (group T) compared to the supine group (group S). In group T, 26.6% had a sensory block level above T8, whereas in group S, 86.6% of patients had a sensory block level above T8. No hypotension was observed in the Trendelenburg group, which was present in 33% of patients in the supine group (group S). CONCLUSION: Ten-degree reverse Trendelenburg position immediately after giving spinal anesthesia significantly limits the level of sensory block and provides better hemodynamic stability, and can be more beneficial, especially in geriatric patients and other high-risk patients for lower limb surgeries.

The Etiology of Anemia Among Pregnant Women in the Hill State of Himachal Pradesh in North India: A Cross-Sectional Study.

Background and objective Anemia during pregnancy is a major cause of maternal and fetal complications including mortality. A study of the etiology of anemia is required to formulate guidelines for the prevention and treatment of the condition. To this end, we conducted a study among anemic women in northern India. Materials and methods A cross-sectional study was conducted among anemic antenatal women attending the outpatient department at a tertiary care hospital in Himachal Pradesh, India, involving 172 participants. Complete blood count, serum ferritin level, serum B12, serum folate levels, high-performance liquid chromatography (HPLC), liver function tests, and renal function tests were performed. Results The mean hemoglobin level among the subjects was 8.87 g/dl with a standard deviation of 0.79; 50% of women had serum ferritin levels of less than 15 ng/ml, 48.8% had serum B12 levels of less than 150 pg/ml. and 33.72% of women had serum folate levels of less than 3 ng/ml. Of note, 13.37% of women had either low or deficient levels for all three parameters; 14 women had abnormal results on HPLC. All nutrient deficiencies (ferritin, folate, and vitamin B12) were found in all morphological types of anemia. Significantly, 73.26% of iron-deficient anemic women had additional folate or vitamin B12 deficiencies, suggesting that additional methods would be required to decrease the prevalence of anemia. Two-thirds of the women in our study were vegetarians, a contributing factor towards a high percentage of vitamin B12 deficiency among women. ß-thalassemia trait was the most common abnormality found, consistent with the high prevalence of ß-thalassemia in north India. Conclusion Multiple deficiencies should be treated simultaneously in anemic women. Vitamin B12 deficiency is an important contributor to anemia, in addition to iron and folate deficiency.

Surveillance of adverse drug reactions at an adverse drug reaction monitoring centre in Central India: a 7-year surveillance study.

OBJECTIVES: To analyse and present the occurrence and severity of spontaneous adverse drug reaction (ADR) reports prospectively registered at an ADR monitoring centre (AMC) in Central India. SETTING AND DATA: The survey was conducted between 2013 and 2019 at an ADR Monitoring Centre in Central India. ADRs were recorded using the standard 'Suspected ADR Reporting form'. OUTCOME MEASURES: The causality of the ADRs were categorised using the WHO causality assessment scale to assess the relationship between a drug and the occurrence of an ADR. RESULTS: Totally 1980 spontaneous ADRs were reported involving 960 patients and 1316 drugs prescriptions. The occurrence of ADRs was common among male patients (64%) and patients of age between 19 and 65 years (81%). Antimicrobials caused 29% ADRs, followed by drugs of antiretroviral therapy (19%). Zidovudine caused most ADRs (88%) followed by ethambutol and ciprofloxacin. The ADRs of skin and subcutaneous tissue disorders (28%) were most common among all system organ classes followed by gastrointestinal systems (18%). Four per cent of all reported ADRs were severe. A peak of ADR reports was attained in 2016 with 224 reports, which decreased to 127 in 2019. CONCLUSION: A high number of ADRs caused by antimicrobials is an alarming situation, which adds up to antimicrobial resistance. Judicious use of antimicrobials is yet again proven as need of the hour. Under-reporting of ADRs is evident in our study and is a major factor for the delay in the withdrawal of drugs responsible for causing ADRs. Interventions in terms of training and feedback are suggested to encourage and improve ADR reporting.

Endothelial Nitric Oxide Synthase (Glu298Asp) Polymorphism is Associated Significantly with Ischemic Stroke Presenting with Seizures and Altered Sensorium.

BACKGROUND: Endothelial nitric oxide synthase (eNOS) is an enzymatic marker whose genetic polymorphism might predispose to acute ischemic stroke (AIS) via vascular endothelial dysfunction. It has a potential role in atherosclerosis, making it a plausible risk factor for stroke. Prior studies have failed to prove a conclusive relationship between eNOS polymorphism and AIS. OBJECTIVE: The aim of this study is to find an association between the presence of eNOS polymorphism (Glu298Asp) and the risk of developing AIS. MATERIALS AND METHODS: We recruited 307 subjects including 153 AIS cases and 154 healthy controls. The eNOS (Glu298Asp) polymorphism was identified in EDTA blood by PCR amplification of the target region followed by restriction enzyme digestion, and genotyping on Agarose gel. GG, GT and TT genotypes were obtained. Statistical analysis was done using SPSS software version 20. RESULTS: A significant association was found between the presence of TT genotype and the risk of AIS (Odd's ratio (OR): 2.43, P-value = 0.038). There was no significant association between the TT genotype and the traditional stroke risk factors. However, the TT genotype was significantly associated with the presence of altered consciousness (OR: 5.27, 95% CI: 1.59-17.04, P-value = 0.003) and with the occurrence of seizures at presentation (OR: 7.98, 95% CI: 1.99-32.09, P-value = 0.007). CONCLUSIONS: There is a significant association between the presence of eNOSpolymorphism (Glu298Asp) and the risk of AIS, and the TT genotype may predispose to a more severe initial presentation of ischemic stroke.

Association of angiotensinogen gene SNPs and haplotypes with risk of hypertension in eastern Indian population.

BACKGROUND: Angiotensinogen (AGT) enzyme comprises a vital module of RAAS system that effectively controls the blood pressure and related cardiovascular functions. Ample association studies have reported the importance of AGT variants in cardiovascular and non-cardiovascular adversities. But lately, owing to the complexity of the many anomalies, the haplotype based examination of genetic variation that facilitates the identification of polymorphic sites which are located in the vicinity of the causative polymorphic site, gets greater appreciation. METHODS: In the present study, we have done genotype and haplotype analysis of AGT gene in reference to hypertension to confirm the association of the two in an Indian population. To accomplish this, we performed candidate SNPs analysis and construct possible haplotypes across the AGT promoter and gene region in 414 subjects (256 Hypertensive cases and 158 controls). RESULTS: We found four SNPs (rs11568020: A-152G and rs5050: A-20C in promoter; rs4762 and rs699 in exon2) and 3 haplotypes (H4, H7 and H8) that showed a stronger positive association with hypertension. The haplotype H2 was showing protective association with hypertension. CONCLUSION: The results of the present study confirmed and reestablished the role of AGT gene variants and their haplotypes in the causation of hypertension in Indian population and showed that haplotypes can provide stronger evidence of association.

Beneficial role of D allele in controlling ACE levels: a study among Brahmins of north India.

India being a country with vast diversity is expected to have different dietary and life style patterns which in turn may lead to population-specific environmental risk factors. Further, the interaction of these risk factors with the genetic makeup of population makes it either susceptible or resistant to cardiovascular disease. One such candidate gene is angiotensin converting enzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone system pathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associated with various complex diseases. The DD genotype is found to increase ACE levels, which is associated with cardiovascular diseases and decrease in ACE levels are associated with kidney diseases. The aim of this study was to understand the distribution of ACE I/D polymorphism and ACE levels among Brahmins of National Capital Region (NCR) north India, with respect to age and sex ratio distribution. In this study, 136 subjects of which 50 males and 86 females, who were unrelated up to first cousin, aged 25 to70 years were studied. ACE gene was found to be polymorphic with high frequency of heterozygote (ID) followed by II and DD genotypes. The studied population was found to be in Hardy-Weinberg equilibrium with respect to ACE I/D polymorphism (P = 0.55). I allele frequency was found to be higher (0.560) than the D allele (0.44). The median level of ACE was found to be 65.96 ng/mL (48.12-86.24) which is towards lower side of the normal range. ACE levels were found to be increased among individual having either of the homozygotes that is II or DD and higher frequency of heterozygote (ID) is indicative of advantage in the population by maintaining lower ACE levels. The limitation of the present study is low sample size, however, the merit is that the subjects belonged to a Mendalian population with a common gene pool.

In silico and bio assay of juvenile hormone analogs as an insect growth regulator against Galleria mellonella (wax moth) - Part I.

Juvenile hormone (JH) analogs are nowadays in use to control harmful pests. In order to develop new bioactive molecules as potential pesticides, we have incorporated different active structural features like sulfonamide, aromatic rings, amide group, and amino acid moiety to the base structure. We have screened a series of designed novel JH analogs against JH receptor protein (jhbpGm-2RCK) of Galleria mellonella in comparison to commercial insect growth regulators (IGRs) - Pyriproxyfen (T1) and Fenoxycarb (T2). All analogs exhibit the binding energy profile comparable to commercial IGRs. Based upon these results, a series of sulfonamide-based JHAs (T3-T8) as IGRs have been synthesized and characterized. Further, the efficacy of synthesized analogs (T3-T8) and commercial IGRs (Pyriproxyfen and Fenoxycarb) has been assessed against fourth instars larvae of G. mellonella under the laboratory conditions. LC50 values of all the analogs (T1-T8) against the fourth instars larvae were 9.99, 10.12, 24.76, 30.73, 38.45, 34.15, 34.14, 19.48 ppm and the LC90 153.27, 131.69, 112.15, 191.46, 427.02, 167.13, 217.10, 172.00 ppm, respectively. Among these analogs, N-(1-isopropyl-2-oxo-3-aza-3-N-ethyl-pentanyl)-p-toluene sulfonamide (T8) and N-(1-isopropyl-2-oxo-3-aza-3-N-ethyl-pentanyl) benzene sulfonamide (T7) exhibited the good pest larval mortality at different exposure periods (in hours) and different concentrations (in ppm) in comparison to in use IGRs- T1 and T2. Bio assay results are supported by docking at higher concentration. The present investigation clearly exhibits that analog T8 could serve as a potential IGR in comparison to in use IGRs (T1 and T2). The results are promising and provide new array of synthetic chemicals that may be utilized as IGRs.

Synthesis, Characterization, Biological Evaluation and Docking Study of Heterocyclic-Based Synthetic Sulfonamides as Potential Pesticide Against G. mellonella.

Juvenile hormone is an important hormone which controls the developmental process in the lepidopteran insects, hence, referred as insect growth regulator. Juvenile hormone binding proteins are the carrier of juvenile hormone from the site of secretion to the site of action and play vital role in juvenile hormone action. We have designed four different juvenile hormone analogs incorporating sulfonamide and heterocyclic moieties using computer-aided tools. All analogs (T3-T6) gave comparative energy profile in comparison to in use insect growth regulators like fenoxycarb (T2) and pyriproxyfen (T1). Further, theses analogs have been screened on biological model Galleria mellonella (wax moth) for their mortality rate. All analogs were evaluated using three different concentrations (1000, 1500, and 2000 ppm) and five different exposure periods (2, 4, 6, 8, and 10 h). In vivo study showed that analog N-(1-isopropyl-2-oxo-2-morpholino-ethyl) toluene sulfonamide (T6) and N-(1-isopropyl-2-oxo-2-piperidino-ethyl) toluene sulfonamide (T4) exhibit the good larval mortality at lower concentration (1000 ppm) after 8 h exposure in comparison to pyriproxyfen (T1) and fenoxycarb (T2). The findings demonstrate the effectiveness and validity of the virtual screening approach (docking) and provide a starting point for the development of novel juvenile hormone analogs to counter G. mellonella.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism among Gaddi tribe of Indian state of Himachal Pradesh.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been suggested to be positively associated with several disorders. Distribution of the mutant T-allele varies in ethnic and geographical populations of the world. AIM: The aim of the present study was to investigate the distribution of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in a transhumant (Gaddi) tribal population of Himachal Pradesh dwelling at high and middle altitude and exposed to strong ultraviolet radiation. METHOD AND RESULTS: A total of 486 samples (141 males and 345 females) were randomly enrolled from the individuals aged 25-75 years who were unrelated up to first cousin. Among Gaddis, genotype frequencies of CC, CT and TT were 67.90%, 27.78% and 4.32%, respectively. Among males and females distribution of genotype frequencies also followed a similar trend. The studied population was in Hardy-Weinberg equilibrium (χ(2 )= 2.213, df = 1, p = 0.136). Frequency of mutant T-allele in the Gaddi population was found to be 0.183, which might be due to European ancestry, endogamous nature and selection.