Ajs Bhanwer

Genomic diversities and affinities among four endogamous groups of Punjab (India) based on autosomal and mitochondrial DNA polymorphisms.

Nineteen insertion/deletion and restriction site polymorphisms on autosomal and mitochondrial genomes and mitochondrial DNA hypervariable segment 1 sequences were used to study genetic diversities and affinities among four endogamous groups of Punjab, India. High values of heterozygosity were noted in all four groups, both in the autosomal and mitochondrial genomes. The coefficient of gene differentiation among the groups, however, was found to be low. Genetic distance and phylogenetic analyses based on these data indicated that inferences on affinities among the populations were different when the two sets of loci (autosomal and mitochondrial) were considered separately. We have interpreted these results on the basis of some known historical data on migrations into this region. The results of this study when compared with the findings of some previous studies indicate that there are regional differences in the patterns of correlation between genomic and sociocultural affinities within India.

TNF-α (g.−308 G > A) and ADIPOQ (g. + 45 T > G) Gene Polymorphisms in Type 2 Diabetes and Microvascular Complications in the Region of Punjab (North–West India)

Abstract Aims: The present study aims to examine the association of tumor necrosis factor-α (TNF-α) g.−308 G > A and adiponectin (ADIPOQ) g. + 45 T > G gene polymorphisms in type 2 diabetes (T2D) and its microvascular complications diabetic retinopathy (DR) and diabetic nephropathy (DN). Materials and Methods: A total of 672 individuals were analysed from the North–West population of Punjab. Genotyping was accomplished by a combination of allele specific amplification refractory mutation system and restriction digestion for TNF-α g. − 308 G > A and ADIPOQ g. + 45 T > G polymorphisms, respectively. Further, in silico modeling was done to predict secondary structure of mRNA for g. + 45 T > G polymorphism in the ADIPOQ gene by RNA fold. Results: The minor allele frequency observed in the controls for the TNF-α G > A and ADIPOQ T > G polymorphisms were 0.07 and 0.10, respectively. The results show no significant association with TNF-α g. − 308 G > A polymorphism in T2D as well as in any of the microvascular complication. However, the ADIPOQ g. + 45 T > G polymorphism shows significant association in T2D (p = 0.048) and DR (p = 0.001) but in DN patients, no association was observed. Interactive analysis revealed that the two polymorphisms jointly conferred a 1.45-fold risk towards the occurrence of T2D [p = 0.031; OR = 1.45 (1.03–2.05)]. In the secondary structure of mRNA, slight free energy change was observed between the wild ( − 1370.28 kcal/mol) and variant allele (−1369.08 kcal/mol). Conclusions: Our results indicated a higher risk of T2D and DR in the background of ADIPOQ TT genotype. Further, the ADIPOQ g. + 45 T > G and TNF-α g. − 308 G > A polymorphisms jointly give 1.45-fold risk towards T2D.

Genomic diversity and affinities in population groups of North West India: An analysis of Alu insertion and a single nucleotide polymorphism

The North West region of India is extremely important to understand the peopling of India, as it acted as a corridor to the foreign invaders from Eurasia and Central Asia. A series of these invasions along with multiple migrations led to intermixture of variable populations, strongly contributing to genetic variations. The present investigation was designed to explore the genetic diversities and affinities among the five major ethnic groups from North West India; Brahmin, Jat Sikh, Bania, Rajput and Gujjar. A total of 327 individuals of the abovementioned ethnic groups were analyzed for 4 Alu insertion marker loci (ACE, PV92, APO and D1) and a Single Nucleotide Polymorphism (SNP) rs2234693 in the intronic region of the ESR1 gene. Statistical analysis was performed to interpret the genetic structure and diversity of the population groups. Genotypes for ACE, APO, ESR1 and PV92 loci were found to be in Hardy-Weinberg equilibrium in all the ethnic groups, while significant departures were observed at the D1 locus in every investigated population after Bonferronis correction. The average heterozygosity for all the loci in these ethnic groups was fairly substantial ranging from 0.3927 ± 0.1877 to 0.4333 ± 0.1416. Inbreeding coefficient indicated an overall 10% decrease in heterozygosity in these North West Indian populations. The gene differentiation among the populations was observed to be of the order of 0.013. Genetic distance estimates revealed that Gujjars were close to Banias and Jat Sikhs were close to Rajputs. Overall the study favored the recent division of the populations of North West India into largely endogamous groups. It was observed that the populations of North West India represent a more or less homogenous genetic entity, owing to their common ancestral history as well as geographical proximity.

Association of Transforming Growth Factor Beta-1 (TGF-β1) Genetic Variation with Type 2 Diabetes and End Stage Renal Disease in Two Large Population Samples from North India

Geographic and ethnic differences impart an immense influence on the genetic susceptibility to Type 2 diabetes (T2D) and diabetic nephropathy (DN). Transforming growth factor-beta1 (TGF-β1), a ubiquitously expressed pro-fibrotic cytokine plays a pivotal role in mediating the hypertrophic and fibrotic manifestations of DN. The present study is aimed to study the association of TGF-β1 g.869T>C (rs1800470) and g.-509C>T (rs1800469) polymorphism in T2D and end stage renal disease (ESRD) cases from the two geographically and ethnically different populations from North India. A total of 1313 samples comprising 776 samples from Punjab (204 with ESRD, 257 without ESRD, and 315 healthy controls) and 537 samples from Jammu and Kashmir (150 with ESRD, 187 without ESRD, and 200 controls) were genotyped for TGF-β1 (rs1800470 and rs1800469) using ARMS-PCR. The CC genotype of rs1800470 increased ESRD risk by 3.1-4.5-fold in both populations. However, for rs1800469, the TT genotype provided 5.5-fold risk towards ESRD cases from Jammu and Kashmir and no risk for the cases from Punjab. The haplotype C-T conferred nearly a 2-3-fold risk towards T2D and ESRD and diplotype CC-CT conferred a 4-fold risk towards ESRD. Our results conclude that TGF-β1 (rs1800470) may increase the risk of both ESRD and T2D in both populations, but TGF-β1 (rs1800469) provided risk for only ESRD in the population of Jammu and Kashmir. The present study is one of the large sample sized genetic association studies of T2D and ESRD from Indian population and adds to the scholarship on global health omics.

Association Study of Angiotensin-Converting Enzyme Ins/Del Polymorphism with Hypertension in Punjabi Population

Abstract Angiotensin-converting enzyme (ACE) is the key enzyme of the Renin-angiotensin system (RAS) which maintains the blood pressure homeostasis in our body. The association of the ACE insertion (I) or deletion (D) with essential hypertension has been demonstrated by many studies. The present study is aimed to determine the association, if any, of ACE I/D polymorphism with essential hypertension in Punjabi population. The ACE I/D polymorphism genotype frequencies were calculated by comparing essential hypertensive patients with ethnically similar normotensive controls. The samples were collected from the outpatient departments of various hospitals of Punjab. The subjects who had systolic blood pressure (SBP) of 140 mmHg or greater, and diastolic blood pressure (DBP) of 90 mmHg or greater, or were using any antihypertensive medication were considered as hypertensive. The DNA samples from the patients (100) and controls (100) were isolated, amplified by PCR and analyzed on agarose gel. When all the genotypes were compared in patients and controls, the chi square value was 0.444, which was not significant at 5% level. The age, height and weight were analyzed in the three different categories DD, ID, II which did not show any significant relationship with the disease. A consistent increase was seen in the SBP and DBP in all the three genotypes from DD, ID to II respectively. This increase was statistically significant for DBP especially in case of DD vs II at 5% level (t=2.34, p<0.05).

Association of genetic variants in INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) with type 2 diabetes (T2D): a case–control study in three ethnic groups from North-West India

Genetic contributions towards Type 2 diabetes (T2D) have been assessed through association studies across different world populations with inconsistencies. The majority of the T2D susceptibility loci are common across different races or populations but show ethnicity-specific differences. The pathogenesis of T2D involves genetic variants in the candidate genes. The interactions between the genes involved in insulin signaling and secretory pathways are believed to play an important role in determining an individual’s susceptibility towards T2D. Therefore, the present study was initiated to examine the differences, if any, in the contribution of polymorphisms towards T2D susceptibility in the background of different ethnic specifications. The present case–control study included a total of 1216 T2D cases and healthy controls from three ethnic groups (Jat Sikhs, Banias and Brahmins) of North-West India. Polymorphisms were selected on the basis of information available in the literature for INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) in context to T2D. The genotyping was done using PCR–RFLP method. Statistical analysis was done using SPSS 16.0. The analyses revealed that INS (rs689) polymorphism conferred risk towards T2D susceptibility in all the three ethnic groups whereas INSR (rs1799816) polymorphism conferred risk towards T2D in Brahmins only and PP1G.G (rs1799999) polymorphism indicated T2D risk in Jat Sikhs only. Furthermore, interaction analyses indicated the cumulative role of three genetic variants in modulating T2D susceptibility in the three ethnic groups. In conclusion, our results substantiated the evidences for the role of ethnicity in differential susceptibility to T2D in the background of same genetic variants.

Study of YAP Element among an Endogamous Human Isolate in Punjab

Abstract The blood samples of 66 Ahmadiyya Muslim males from Qadian, district Gurdaspur of Punjab have been analysed to study the Y-chromosome Alu insertion polymorphism (YAP). Y-chromosomes carrying the YAP element were found in many populations in India and Pakistan. However, the absence of YAP insertion element in the present Ahmadiyya population has suggested that this isolated population is not likely to have been affected by many migrations in Indian history.

Study of DYS 390 Polymorphism among Khatri Population of Punjab in Comparison to Other Indian and World Population

Abstract The Y chromosome specific polymorphism (Y-STR and Y-SNPs) can be used to track paternal lineages as well as male specific movements and admixture among humans. The objective of the present work is to study the genetic polymorphism at Y chromosome specific STR locus, DYS390 among Khatri population of Punjab and generate a comparative data with respect to other Indian and world populations. The DNA was isolated from blood samples of Khatri male individuals through organic method and were amplified by PCR using specific primers for DYS390 locus. The PCR products were electrophoresed on polyacrylamide gels and silver staining was done to resolve and observe different alleles. Gel-Pro 3.1 software was used to confirm the allele size. Chi-Square test was applied to test whether differences between the allele frequencies among Khatri, other Indian and world populations were statistically significant. Network Joining (NJ) tree was constructed using Network analysis software. The results showed 7 different alleles ranging from 22 to 28 in Khatri population and revealed a significantly high degree of genetic heterogeneity at this locus. The gene diversity was found to be 0.8363. The Network Joining tree showed Khatri population as an independent branch alongside Chinese. Therefore, it can be inferred that Khatri population is probably a result of conglomeration of different lineages, like most other North-West Indian population.

Associating genetic variation at Perilipin 1, Complement Factor D and Adiponectin loci to the bone health status in North Indian population

Osteoporosis, the most common bone metabolic disease affecting nearly 200 million people worldwide is under the strong influence of genetic components. Simultaneously, adipogenesis and osteogenesis are two highly coordinated processes imperative for the maintenance of bone quality and quantity, where any perturbation leads to pathological conditions of obesity, osteopenia and osteoporosis. To delineate this adipogenic-osteogenic connection, a total of 254 cases (T-score<-1.0 SD) and 250 age, gender and ethnicity matched healthy controls (T-score≥-1.0 SD) were recruited from North India after analyzing bone health status employing quantitative ultrasound (QUS) bone densitometer. The genetic variants of Perilipin 1 (PLIN1), Complement Factor D (CFD) and Adiponectin (ADIPOQ) were genotyped using the PCR-RFLP/ARMS-PCR approach. Subjects with CC+CT (PLIN1 rs2304795) and CC+CG (CFD rs1683563) genotypes conferred nearly 1.54-1.87 fold increased risk towards bone deterioration. Predicted RNA secondary structures of rs2304795 corroborated the risk associated with wild type C allele. G allele carriers at the ADIPOQ locus (rs1501299) were more likely to have a lower bone health (1.57-fold). Haplotype analysis revealed the ADIPOQ variants rs1501299 and rs3774261 in slight linkage disequilibrium (LD), nonetheless G/G haplotype was associated with increased risk. 3-locus and 5-locus gene-gene interaction models revealed a greater likelihood of bone deterioration. In conclusion, certain variants of adipogenic genes might serve as potential biomarkers for determining the genetic predisposition towards bone loss in the North Indian population, further, emphasizing the role of impaired metabolism in bone health.