Saliha Rizvi

Association of genetic variants with diabetic nephropathy

Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, eNOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.

Telomere Length Variations in Aging and Age-Related Diseases

Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimers disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

Association of Genetic polymorphism of PPARγ-2, ACE, MTHFR, FABP-2 and FTO genes in risk prediction of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a non-autoimmune, complex, heterogeneous and polygenic metabolic disease condition characterized by persistent elevated blood glucose levels (hyperglycemia). India as said to be the diabetic capital of the world is likely to experience the largest increase in T2DM and a greater number of diabetic individuals in the world by the year 2030. Identification of specific genetic variations in a particular ethnic group has a critical role in understanding the risk of developing T2DM in a much efficient way in future. These genetic variations include numerous types of polymorphisms among which single nucleotide polymorphisms (SNPs) is the most frequent. SNPs are basically located within the regulatory elements of several gene sequences. There are scores of genes interacting with various environmental factors affecting various pathways and sometimes even the whole signalling network that cause diseases like T2DM. This review discusses the biomarkers for early risk prediction of T2DM. Such predictions could be used in order to understand the pathogenesis of T2DM and to better diagnostics, treatment, and eventually prevention.

Polymorphism of GST and FTO Genes in Risk Prediction of Cataract among a North Indian Population.

Abstract Background: The present study was carried out to investigate the association of GST and FTO gene polymorphisms with cataract cases and controls. Materials and methods: The study included 131 cases and 126 controls. GST and FTO gene polymorphisms were evaluated by PCR-RFLP. Results: The frequency of the GSTM1-positive and GSTT1-positive in cataract cases were 62.13% and 86.40% while in the controls it was 46.39% and 95.87% with odds ratios of 1.9 (95% CI, 1.08–3.32; p value 0.025) and 0.27 (95% CI, 0.09–0.86; p value, 0.019) respectively. There was a statistically significant association between the GSTM1 null genotype and the risk of cataract development with an odds ratio of 0.43 (95% CI, 0.24–0.76; p value, 0.003). Significant differences were obtained in the frequencies of FTO AA and TT genotype (p = 0.023 and 0.023) between cases and controls. Conclusion: The present study suggested that GSTM1, GSTT1 and FTO gene polymorphisms are associated with increased risk for cataract in North Indian populations. Due to the limited sample size, the finding on GST and FTO gene polymorphisms need further investigation.

Role of GNB3, NET, KCNJ11, TCF7L2 and GRL genes single nucleotide polymorphism in the risk prediction of type 2 diabetes mellitus

Type 2 diabetes (T2DM) is a polygenic metabolic disorder characterized by hyperglycemia occurring as a result of impaired insulin secretion or insulin resistance. Various environmental and genetic factors interact and increase the risk of T2DM and its complications. Among the various genetic factors associated with T2DM, single nucleotide polymorphism in different candidate genes have been studied intensively and the resulting genetic variants have been found to have either positive or negative association with T2DM thereby increasing or decreasing the risk of T2DM, respectively. In this review, we will focus on Guanine nucleotide-binding protein subunit beta 3 (GNB3), Norepinephrine Transporter (NET), Potassium Channel gene (KCNJ11), Transcription Factor 7-Like 2 (TCF7L2) and Glucocorticoid receptor (GRL) genes and their association with T2DM studied in different ethnic groups. The products of these genes are involved in the biochemical pathway leading to T2DM. Polymorphisms in these genes have been intensively studied in individuals of different ethnic origins. Results show that genetic variants of TCF7L2 and KCNJ11 genes have potential to emerge as a risk biomarker for T2DM whereas results of GNB3, GRL and NET genes have been controversial when studied in individuals of different ethnicities. We have tried to summarize the results generated globally in context to the selected genes which could possibly help researchers working in this field and would eventually help in understanding the mechanistic pathways of T2DM leading early diagnosis and prevention.

Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population

Abstract Background: Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. Aim: The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls. Subjects and methods: This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method. Results: Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls. Conclusion: It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.

Polymorphism of FABP2 and PPARG2 genes in risk prediction of cataract among North Indian population.

Background Cataract is the leading cause of bilateral blindness in India. It has been reported that cataract is responsible for 50–80% of the bilaterally blind in the country. Cataract formation is a natural part of the ageing process. At present, adequate data are not available regarding the FABP2 and PPARG2 gene polymorphisms and their susceptibility with cataract cases in the North Indian population. Thus, the present study was carried out to investigate the association of FABP2 and PPARG2 gene polymorphisms with cataract cases and controls. Materials and methods This study includes 130 cataract cases and 118 controls. FABP2 and PPARG2 gene polymorphisms in cases and controls were evaluated by PCR-RFLP. Results Frequencies of Ala54Ala, Ala54Thr and Thr54Thr genotypes in FABP2 gene in cataract cases and controls were 50.76%, 39.23%, 10% and 25.42%, 61.86%, 12.71% respectively. The PPARG2 gene CC, CG, GG genotype frequencies were 11.53%, 87.69% and 0.76% in cases and 21.18%, 39.83% and 38.98% in healthy controls respectively. Significant differences were observed in the frequencies of FABP2 Ala54Ala, Ala54Thr genotype (p < 0.05) and PPARG2 CC, CG, GG genotype (p < 0.05) between cases and controls. Conclusion The findings of this study suggest that FABP2 and PPARG2 gene polymorphisms can be an informative marker for early identification of population at risk of cataract. The potential role of FABP2 and PPARG2 gene polymorphisms as a marker of susceptibility to cataract needs further studies in a larger number of patients.

Genetic polymorphism in KCNJ11 (E23K, rs5219) and SDF-1β (G801A, rs1801157) genes are associated with the risk of Type 2 diabetes mellitus

Abstract Background Type 2 diabetes mellitus (T2DM) is a global major health problem resulting from interaction of environmental and genetic factors, examples of the latter being KCNJ11 (coding for part of the ATP-sensitive potassium channel) and SDF-1β (coding for chemokine CXCL12). Our case-control study was conducted to assess whether recessive, dominant or additive genotype model associations of KCNJ11 (E23K, rs5219) and SDF-1β (G801A, rs1801157) were more strongly linked to type 2 diabetes. Subjects & Methods Genetic polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism. Alleles and genotype frequencies between 200 cases and 200 controls were determined and compared. Results The dominant (EE v EK + KK, p = 0.022) and additive (EK v EE + KK, p = 0.021) models, but not the recessive model (KK v EE + EK, p = 0.727) of KCNJ11 were linked to diabetes. Similarly, the dominant (GG v GA + AA, p < 0.001) and additive (AG v GG + AA, p=<0.001) models, but not the recessive model (AA v AG + GG, p = 0.430) of SDF-1β were linked to diabetes. The A allele (p = 0.006) of SDF-1β was protective against the risk of T2DM. Conclusion Both dominant and additive models in both KCNJ11 (E23K, rs5219) and SDF-1β (G801A, rs1801157) genetic polymorphisms are significantly associated with type 2 diabetes.

The relationship between Multidrug Resistance Protein 1(rs1045642) and Cholesterol 24-hydroxylase (rs754203) genes polymorphism with type 2 diabetes mellitus

Abstract Background: The involvement of genetic factors like gene polymorphisms has been found to contribute significantly to the development and progression of type 2 diabetes (T2DM). Thousands of single nucleotide polymorphisms in various genes have been found to be associated with risk of T2DM. The present study was aimed to investigate association of Multidrug resistance 1 (MDR1) (rs1045642) and CYP46A1 (rs754203) genes polymorphism with T2DM. Subjects & Methods: Study includes 333 subjects, 183 T2DM cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by PCR-PFLP. Alleles and genotype frequencies between cases and controls were compared using χ2 and Student’s t-tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. Results: In case of CYP46A1 gene, CC (p < 0.001) and CT (p = 0.001) genotypes and C allele (p < 0.001) were found to be a positive risk factor and TT genotype (p < 0.001) and T allele (p < 0.001) as negative risk factor for T2DM whereas, no association of MDR1 gene was found with T2DM (P values of all genotypes and alleles were greater than 0.001). MDR1 (rs1045642) and CYP46A1 (rs754203) genes polymorphism was not found associated with Fasting Blood Sugar (FBS), Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP). Conclusion: CYP46A1 gene polymorphism is associated with the risk of T2DM whereas, MDR1 gene polymorphism was not found to confer any risk of T2DM in North Indian Ethnic group.

Association of Angiotensin-Converting Enzyme and Glutathione S-Transferase Gene Polymorphisms with Body Mass Index among Hypertensive North Indians

OBJECTIVES This study aimed to examine the association of angiotensin-converting enzyme (ACE) and glutathione S-transferase (GST) gene polymorphisms with body mass index (BMI) in hypertensive North Indians. METHODS This case-control study was carried out between May 2013 and November 2014 at the Eras Lucknow Medical College & Hospital, Lucknow, India, and included 378 subjects divided into three groups. One group constituted 253 hypertensive individuals (sustained diastolic blood pressure of >90 mmHg and systolic blood pressure of >140 mmHg) who were subcategorised according to normal (<25 kg/m(2)) or high (≥25 kg/m(2)) BMI. The third group consisted of 125 age-, gender- and ethnically-matched normotensive controls with a normal BMI. Gene polymorphisms were evaluated by polymerase chain reaction. The genotypic and allelic frequency distribution among both groups were analysed. RESULTS A significant difference was found between GST theta 1-null and GST mu 1-positive genotype frequencies among the hypertensive overweight/obese individuals and controls (P = 0.014 and 0.033, respectively). However, no difference was observed in the frequency of ACE polymorphisms. ACE insertion/insertion genotype (P = 0.006), insertion and deletion alleles (P = 0.007 each) and GST theta 1-null and GST theta 1-positive genotypes (P = 0.006 each) were found to differ significantly between hypertensive cases and controls, regardless of BMI. CONCLUSION ACE and GST gene polymorphisms were not associated with BMI but were significantly associated with hypertension among the studied group of North Indians.