Vitamin D, Its Receptor Gene Polymorphism and Breast Cancer

Vitamin D is synthesized within skin followed by the peripheral maturation in liver and kidneys. Vitamin D is most essential secosteroid produced its systemic functions via complex with steroid/thyroid nuclear receptor called vitamin D receptor (VDR). The binding of the vitamin D3 to VDR causes conformational changes that permit VDR-RXR heterodimer formation and VDR/ SRC-1 (transcriptional co-activator proteins) interactions. Functional expression and nuclear activation of VDR is necessary to produce its effects upon binding with vitamin D response element (VDRE) on target gene where it causes transcriptional activation resulting in the prevention of breast cancer by inhibiting proliferation, impeding differentiation and stimulating pro-apoptosis. Season, latitude, pigmentation of skin, aging, sunscreen use, obesity, and smoking all affect the production of vitamin D. In case of vitamin D deficiency or VDR gene polymorphisms, vitamin D responses are altered and probably are involved in the risk of breast cancer. Since many epidemiological, observational and interventional studies have been done to illustrate the role of vitamin D and its receptor gene polymorphism in breast cancer development but controversial findings have been observed. Therefore, the role of vitamin D and its receptor gene polymorphisms in development of breast cancer are still a matter of discussion

Genetic Variations of Brain Derived Neurotropic Factor Gene With Premenstrual Syndrome Among Pakistani Menarcheal Girls: A Pilot Study

The premenstrual syndrome (PMS) comprises various physical and emotional symptoms which are associated with the menstrual cycle. The emotional changes might be due to the variation in the levels of BDNF especially lower levels of plasma BDNF may be present at the luteal phase of menstrual cycle. To date, no data were present to associate the link between BDNF gene polymorphism and PMS among young Menarcheal females. So, the goal of this investigation is to find out the possible relationship between BDNF gene polymorphism and PMS among young Menarcheal females of Pakistan. A total of 92 menarcheal girls with age range of 11-14yrs met the inclusion criteria. All participants were screened for the depression and PMS using Zung’s depression scale/ Diagnostic and Statistical Manual of Mental Disorders-IV (DSM IV) criteria and world health organization (WHO) criteria for PMS respectively. Genomic DNA was extracted from oral samples by Salting out method and BDNF genotyping was done using PCR-RFLP analysis. Results showed no significant association (χ2=1.685, p-value=0.431) was observed between BDNF genotyping and PMS among menarcheal girls. BDNF (rs6265) AA and GA genotypes did not show significant association with the risk of PMS. Hence, it was concluded that BDNF gene polymorphism may not be associated with the PMS among Pakistani Menarcheal girl

Effects of Maternal Subclinical Hypothyroidism On Neurodevelopment of Offspring- An Animal-Based Study

ABSTRACT Background and objective: Maternal subclinical hypothyroidism (SCH) during pregnancy is associated with adverse maternal and neonatal outcomes, including cognitive and neuropsychiatric effects. This study aimed to assess the impact of maternal SCH on young rats, examining behavioral and gross brain structure changes, and evaluating reversibility after levothyroxine treatment. Methods: This experimental animal study was conducted at the Aga Khan University for a duration of 10 months. The study was approved by the Ethical committee for Animal Care and Use. Fourteen female Sprague Dawley rats were grouped into Treated (induced with SCH, treated with levothyroxine), Untreated (induced with SCH, no treatment), and Control (administered saline). Pups\u27 body weight was monitored, and histological procedures were conducted at postnatal days 7, 14, and 21. Behavioral tests (elevated plus maze, forced swim, and tail suspension) assessed anxiety and depression. The data was analysed using SPSS (version 25.0). The mean, median, and standard deviation were calculated for each quantitative parameter. A one-way ANOVA was performed to identify any variation in mean thyroid levels between groups, and an independent sample t-test was utilized to confirm mean differences in anxiety levels. Results: On postnatal day 7, untreated pups showed lower body weight compared to treated and control groups. This trend continued on days 14 and 21. By day 21, an elevated plus maze (EPM) test indicated anxiety-like behaviour in untreated pups, while they also exhibited more signs of depression in tests like the forced swim test (FST) and tail suspension test (TST). Brain structure, including the prefrontal cortex, remained intact in offspring affected by maternal thyroid dysfunction, with no significant changes observed in brain morphology across the groups. Conclusion: Despite unchanged brain structure, untreated rat pups exhibited significant behavioral differences indicative of depression. This underscores the importance of understanding the behavioral impacts of maternal SCH even in the absence of gross anatomical alterations

Breast Cancer: Impact of Modifiable and Non-Modifiable Risk Factors Among Premenopausal Women of Karachi, Sindh

Objective: The goal of present study was to probe the interplay between modifiable and non-modifiable factors and breast cancer (BC) risk. Methodology: Two hundred and twenty-eight (228) BC cases and 503 healthy volunteers with 20-45years of age without history of BC were recruited from tertiary hospitals located in Karachi, a metropolitan city ofPakistan. Major risk factors for the BC were evaluated using pretested self-structured questionnaire. Results: The adjusted regression analysis showed that Balouchi (OR=12.93, 95%CI=4.26-39.17) and Sindhi (OR=9.41, 95%CI=4.72-18.77) ethnicity, familial history of BC (OR=1.83, 95%CI=1.16-2.91), low socioeconomic status (OR=26.81, 95%CI=17.56-40.94), marital age >30yrs (OR=20.99, 95%CI=4.15-106.24),hormone replacement therapy (OR=1.95, 95%CI=1.03-3.69), being obese (OR=1.589, 95%CI=1.03-2.46),high waist-to-Hip ratio (WHR) (OR=2.69, 95%CI=1.67-4.32), apple shape body (OR=2.62, 95%CI=1.63-4.21), consanguineous marriages (OR=1.62, 95% CI=1.15-2.29) and sun exposure <1 hr/day (OR=7.56,95%CI=3.002-19.04), daily intake of beef (OR = 1.544, 95%CI=1.004-2.373), dry fruits (OR=1.922,95%CI=1.233-2.996), rice (OR= 2.412, 95%CI=1.17-4.973), tea and coffee (OR=2.299, 95%CI=1.246-4.24)and less consumption of milk (OR=1.942, 95%CI=1.344-2.807) and fruits (OR=2.952, 95%CI=1.505-5.792) were increased the BC risk among premenopausal women. Conversely, first pregnancy <24yrs (OR=0.53,95%CI=0.33-0.85), WHR <0.85 (OR=0.296, 95%CI=0.15-0.59), avocado body shape (OR=0.31,95%CI=0.16-0.61), excessive chicken (OR=0.403, 95%CI=0.206-0.791) and eggs (OR=0.479, 95CI=0.304-0.755) consumption were considered a protective factor. Conclusion: Ethnicity, SES, marital age, HRT, breast cancer family history, overweight and obesity,intermarriages and sun exposure may be the major risk factors for BC among premenopausal women of Sindh, Pakistan. Diet may also play a role in developing BC

Interplay of leukemia inhibitory factor receptor gene (rs3099124) polymorphism, leukemia inhibitory factor and ovarian steroids with unexplained infertility

Objective of the study: To explore the association of leukemia inhibitory factor receptor (LIFR) gene variant rs3099124, ovarian steroids, and leukemia inhibitory factor with unexplained infertility in Pakistani females. Methodology: A case-control investigation in which eighty-one (81) females with unexplained infertility and one hundred and sixty-two (162) fertile counterparts (age and body mass index compared) were recruited between October 2016 and 2018. Ten milliliters of venous blood was collected from all participants. Genomic DNA was taken out from lymphocytes in peripheral blood samples. Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR) was constructed through software Primer-I . Amplification was carried out by T-ARMS-PCR followed by subsequent sequencing for confirmation and extensive consonance. Estradiol, Progesterone and Leukemia Inhibitory Factor (LIF) were measured in serum by ELISA. Results: Statistically significant difference was noticed in genotype frequency in LIFR-gene variant; rs3099124 (χ2 = 28.222, P value \u3c 0.01) between research participants. Although, rs 3099124 AA (OR = 0.000; 95%CI = 0-0) and GA genotypes (OR = 0.525; 95%CI = 0.226-1.22) showed non-significant safety/protection against unexplained infertility yet minor/risk allele A frequency was greater in women with unexplained infertility suggesting a possible explanation of implantation failure. LIF concentration varied between fertile and infertile groups (χ2 = 9.857, P \u3c 0.05) revealing significant threat of unexplained infertility in women with decreased LIF concentration (OR = 2.316, 95%CI = 1.214-4.416). Progesterone was significantly related to unexplained infertility in both study groups (χ2 = 20.347, P \u3c 0.05). High progesterone reduced the possibility of unexplained infertility (OR = 0.306; 95% CI = 0.166-0.567). Conclusion: LIFR gene variation (rs3099124) and reduced LIF secretion may cause implantation failure in women with unexplained infertilit

A Functional Polymorphism (rs6265, G>A) of Brain-Derived Neurotrophic Factor Gene and Breast Cancer: An Association Study

Purpose: The objective of this study was to evaluate the relationship between brain-derived neurotrophic factor (BDNF) gene (Val66Met, rs6265, G>A) polymorphism and breast cancer (BC) among females of Southern Pakistan. Methods: This case-control study consisted of 300 females (BC cases [n = 100] and controls [n = 200]) with age range of 18 to 45 years. All participants were recruited during January to December 2014 and were screened for depression using Zung depression scale. Isolation of genomic DNA (gDNA) followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was done. All statistical analysis was carried out on IBM-SPSS version 22 at P -value <.05. Hardy-Weinberg equilibrium (HWE), Pearson chi-square, and odds ratios (ORs) with 95% confidence interval (95% CI) were calculated. Results: Genotype distribution of BDNF gene polymorphism lies in the goodness-of-fit model among controls. The statistical analyses reveal a significant association between genotype frequencies (χ 2  = 12.709, P -value = .002) of BDNF and BC among cases and controls. The AA genotype (OR = 5.2, 95%CI = 0.632-42.804) increases the risk of having BC. Conclusions: Our results suggest that BDNF gene polymorphism may have an association with BC risk among Pakistani females. However, the present finding needs to be replicated with greater sample size with BC risk

Association of Visfatin gene polymorphism with obesity related metabolic disorders among Pakistani population: a case control study

Abstract In recent years, the global prevalence of obesity and its associated metabolic disorders has reached alarming levels, presenting a significant challenge to public health worldwide. Visfatin, also known as pre-B cell colony-enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (NAMPT), is an adipokine that has been implicated in various physiological processes, including glucose homeostasis, lipid metabolism, and inflammation. The main objective of this proposed study is to find out the association between visfatin genetic variants and metabolic syndrome. The sample size of the study consisted of 300 blood samples (150 control and 150 cases). This study found that the genotypic frequency of visfatin SNPs, including rs2302559 (OD: 18.222; 95% CI 10.228–32.466; p-value < 0.001) and rs1215113036 (OD: 129.40; 95% CI 44.576–375.693; p-value < 0.001) were significantly associated with metabolic syndrome. Moreover, the frequency of the mutant alleles of both visfatin SNPs was found to be higher in patients with metabolic syndrome as compared to controls. Results of the current study indicate that people with any genetic variation of Visfatin, such as rs2302559 and rs1215113036, are more likely to develop metabolic syndrome. Visfatin genetic variants are linked to an increased risk of metabolic syndrome, implying it’s role in disease pathophysiology