Imran Ali Khan

Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus:

Introduction: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. Insertion/deletion (I/D) polymorphism of a 287 bp Alu repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been widely investigated in Asian Indian populations with different ethnic origins. The present study examined possible association between I/D polymorphism of the ACE gene and GDM in Asian Indian pregnant women. Methods: A total of 200 pregnant women (100 GDM and 100 non-GDM) were recruited in this study and I/D polymorphism of a 287 bp Alu1 element inside intron 16 of the ACE gene was examined by polymerase chain reaction (PCR)-based gel electrophoresis. Result: The distribution of the variants like II, ID, and DD genotypes of ACE gene showed differences between normal GDM versus non-GDM subjects, and the frequency of the ID+ DD Vs II genotype was significant (p=0.0002) in the GDM group. Conclusion: ACE gene polymorphism was associated with GDM in Asian Indian pregnant women.

Investigation of Calpain 10 (rs2975760) gene polymorphism in Asian Indians with Gestational Diabetes Mellitus

Background Type 2 Diabetes Mellitus (T2DM) and Gestational Diabetes Mellitus (GDM) are part of a heterogeneous and complex metabolic group of disorders that share common pathophysiological circumstances, including β-cell dysfunction and insulin resistance. The protein Calpain 10 (CAPN10) plays a role in glucose metabolism, pancreatic β-cell insulin secretion, and thermogenesis. Objective Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP) based genotyping of CAPN10 (rs2975760) polymorphism was carried out in T2DM and GDM with suitable controls for each of the pathologies from the same population. Genomic DNA was isolated from 787 participants, including 250 cases of T2DM, 287 pregnant women, of which 137 were identified as having GDM and the remaining 150 were confirmed as non-GDM, and 250 healthy control volunteers, and association analysis was carried out for genotypes and alleles. Results In the present study, T2DM was compared with healthy controls and was not found to be associated with the CAPN10 C allele (odds ratio, OR: 1.09; 95% CI = 0.8011–1.484; p = 0.5821). GDM also did not show any association when compared with non-GDM (OR: 1.124; 95% CI = 0.7585–1.667; p = 0.5606) respectively. Conclusion Our study suggests that the CAPN10 (rs2975760) polymorphism scrutinized in this study is not associated with T2DM and GDM.

Influence of adiposity-related genetic markers in a population of saudi arabians where other variables influencing obesity may be reduced.

Large scale studies in Europeans have clearly identified common polymorphism affecting BMI and obesity. We undertook a genotype study to examine the impact of variants, known to influence obesity, in a sample from the Saudi Arabian population, notable for its profound combination of low mean physical activity indices and high energy intake. Anthropometry measures and genotypes were obtained for 367 Saudis, taken from King Saud University and Biomarker Screening Project in Riyadh (Riyadh Cohort). We observed large effect sizes with obesity for rs10767664 (BDNF) (OR = 1.923, P = 0.00072) and rs3751812 (FTO) (OR = 1.523, P = 0.016) in our sample and, using weighted genetic risk scores, we found strong evidence of a cumulative effect using 11 SNPs taken predominantly from loci principally affecting appetite (OR = 2.57, P = 0.00092). We used conditional analyses to discern which of our three highly correlated FTO SNPs were responsible for the observed signal, although we were unable to determine with confidence which best marked the causal site. Our analysis indicates that markers located in loci known to influence fat mass through increased appetite affect obesity in Saudi Arabians to an extent possibly greater than in Europeans. Larger scale studies will be necessary to obtain a precise comparison.

A Computational Protein Phenotype Prediction Approach to Analyze the Deleterious Mutations of Human MED12 Gene

Genetic mutations in MED12, a subunit of Mediator complex are seen in a broad spectrum of human diseases. However, the underlying basis of how these pathogenic mutations elicit protein phenotype changes in terms of 3D structure, stability and protein binding sites remains unknown. Therefore, we aimed to investigate the structural and functional impacts of MED12 mutations, using computational methods as an alternate to traditional in vivo and in vitro approaches. The MED12 gene mutations details and their corresponding clinical associations were collected from different databases and by text‐mining. Initially, diverse computational approaches were applied to categorize the different classes of mutations based on their deleterious impact to MED12. Then, protein structures for wild and mutant types built by integrative modeling were analyzed for structural divergence, solvent accessibility, stability, and functional interaction deformities. Finally, this study was able to identify that genetic mutations mapped to exon‐2 region, highly conserved LCEWAV and Catenin domains induce biochemically severe amino acid changes which alters the protein phenotype as well as the stability of MED12‐CYCC interactions. To better understand the deleterious nature of FS‐IDs and Indels, this study asserts the utility of computational screening based on their propensity towards non‐sense mediated decay. Current study findings may help to narrow down the number of MED12 mutations to be screened for mediator complex dysfunction associated genetic diseases. This study supports computational methods as a primary filter to verify the plausible impact of pathogenic mutations based on the perspective of evolution, expression and phenotype of proteins. J. Cell. Biochem. 117: 2023–2035, 2016.

A54T polymorphism in the fatty acid binding protein 2 studies in a Saudi population with type 2 diabetes mellitus

BackgroundFatty acid-binding protein 2 (FABP2) is an intracellular protein expressed exclusively in the enterocytes of proximal small intestine. FABP2 has a high affinity for saturated and unsaturated long-chain fatty acids and is believed to be involved in the absorption and transport of dietary fatty acids.MethodsThis is a case–control study conceded in 438 T2DM cases and 460 subjects with normal glucose levels and non-obese considered as healthy controls. Allelic discrimination was performed using TaqMan single-nucleotide polymorphism was carried out by real time-polymerase chain reaction (RT-PCR) assays using purified DNA.ResultsClinical data and anthropometric measurements except age, glucose levels and lipid profile of the patients were significantly different from those of the controls (p < 0.05). Statistical analyses failed to show any type of significant association of the polymorphism between cases and controls. However logistic regression analyses was suggests that the TT genotype is significantly associated with male patients (p = 0.001). None of the allele or genotypes of FABP2 A54T was associated with T2DM cases versus the controls (AT genotype, OR = 0.85 (0.64-1.12), p = 0.25; TT genotype, OR = 0.66 (0.39-1.11), p = 0.11; T allele, 0.82 (0.67-1.02), p = 0.08).ConclusionIn conclusion, this study suggests that the above named variant in FABP2 gene is not potential contributor to the risk of T2DM and related traits in a Saudi population. However TT genotype is a risk factor for the disease in males.

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DM in a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DM patients (0.28 vs 0.45; p<0.0001; OR (95% CI) = 0.4624 (0.3732–0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.

Evaluation of Aurora-A gene polymorphism and esophageal cancer risk in a South Indian population.

AIM Aurora-A is a serine/threonine protein kinase that functions in centrosome maturation and spindle assembly and is involved in regulating chromosome segregation. It is amplified and overexpressed in several human cancers. The aim of the present study was to assess the role of T91A Aurora-A gene polymorphism associated with aneuploidy in human tumors. RESULT Patients with different upper gastrointestinal tract symptoms who were referred for endoscopy were studied. They were categorized as individuals with esophageal cancer, esophagitis, and normal endoscopy based on endoscopy and histology reports. Healthy volunteers were used as controls for carrying out genomic polymerase chain reaction followed by restriction digestion. The cancer and esophagitis groups showed a higher percentage of cases with the TA genotype compared with the controls and gastrointestinal tract normal endoscopy samples. However, only esophagitis, despite a small sample size, showed a statistically significant association with the TA genotype (odds ratio=3.6082, 95% class interval=1.1276-8.8346, p=0.0411). It was also assessed if the T91A polymorphism plays a role in enhancing the effects of exogenous factors such as smoking, alcohol, tea, betel chewing, and nonvegetarian diet in esophageal pathologies. CONCLUSION Our results indicate that the TT genotype is protective against these factors as a higher percentage of this genotype was found in individuals with normal endoscopy. This is the first study, to the best of our knowledge, carried out in an Indian population to evaluate the association of Aurora-A gene polymorphism with esophageal cancer.

The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population

Introduction: Angiotensin I converting enzyme (ACE) insertion and deletion (I/D) polymorphism has been implicated in the pathogenesis of osteoarthritis (OA). In recent years, numerous genetic factors have been identified and implicated in OA. In this Asian Indian population-based study, we aimed to evaluate the relationship between ACE (I28005D) gene polymorphism and primary OA. We performed a case-control association study to identify and explore the correlation between clinically, radiologically diagnosed individuals with primary knee OA and the ACE I/D polymorphism. Methods: Genomic DNA was isolated from 200 samples, including 100 OA cases and 100 healthy volunteers. DNA was amplified by polymerase chain reaction (PCR) using I and D allele-specific primers. PCR products were assessed via UV visualization of products electrophoresed on 2% agarose gels. Results: The groups differed significantly in genotype distributions (p < 0.05). The primary knee OA group showed a considerably higher incidence of the DD genotype and the D allele compared to the control group (OR = 2.14, 95% CI: 1.10–4.15, p = 0.02 and OR = 2.08, 95% CI: 1.39–3.10, p = 0.0003). Conclusion: The ACE gene polymorphism I28005D was found to be associated with primary knee OA in Asian Indian populations. This is the first study in India to report that the ACE gene polymorphism is a risk factor for early onset primary knee OA.

Relationship between the paraoxonase 1 gene glutamine 192 to arginine polymorphism and gestational diabetes mellitus in Saudi women

OBJECTIVES Gestational diabetes mellitus (GDM) is recognized as an imbalance between insulin resistance and insulin secretion, leading to maternal hyperglycemia. Previous studies in a Saudi population indicated a high frequency of Paraoxonase 1 glutamine 192 to arginine (PON1 Q192R) polymorphism, suggesting this polymorphism as an additional risk factor. The present study was designed to explore the possible association between the PON1 Q192R polymorphism and GDM in a Saudi population. METHODS This case-control study was carried out in 500 pregnant women, including 200 GDM cases and 300 non-GDM women. Genotyping for PON1 Q192R (rs662) variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS The results of the present study indicates that Q192R polymorphism was significantly associated with GDM in a Saudi population with the minor allele frequency (MAF) (p=0.0007). Q192R genotypes and alleles showed a strong association with GDM (p=0.009 and p=0.0007, respectively). CONCLUSION In conclusion, these findings suggest that the PON1 Q192R polymorphism has high MAF in GDM in the studied Saudi population.

Insulin Receptor Substrate-1 (IRS-1) Gly927Arg: Correlation with Gestational Diabetes Mellitus in Saudi Women

Pregnant women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share a common pathophysiology associated with similar risk factors. Genetic variants used to determine the risk of developing T2DM might also be associated with the prevalence of GDM. The aim of the present study was to scrutinize the relationship between the G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene with GDM in the Saudi female population. This is a case-control study that monitored 500 Saudi women. Subjects with GDM (n = 200) were compared with non-GDM (n = 300) controls. We opted to evaluate rs1801278 polymorphism in the IRS1 gene, which plays a critical role in the insulin-signaling pathway. Genotyping was performed with the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The frequency of the rs1801278 polymorphism was significantly higher in women with GDM than in women with non-GDM (for TT + CT versus CC: P = 0.02). Additionally, there was a significant increase in the frequency of the Arg-encoding mutant allele from GDM to non-GDM (for T versus C: P = 0.01). Our results suggest that the rs1801278 polymorphism in the IRS-1 gene is involved in the occurrence of GDM in the Saudi population.