Association of Genetic Variants of KCNJ11 and KCNQ1 Genes with Risk of Type 2 Diabetes Mellitus (T2DM) in the Indian Population: A Case-Control Study.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. The interaction between various genetic variants and environmental factors triggers T2DM. The aim of this study was to find risk associated with genetic variants rs5210 and rs2237895 of KCNJ11 and KCNQ1 genes, respectively, in the development of T2DM in the Indian population. A total number of 300 cases of T2DM and 100 control samples were studied to find the polymorphism in KCNJ11 and KCNQ1 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different compared to the control population. KCNJ11 rs5210 and KCNQ1 rs2237895 variants were found to be significantly associated with risk of T2DM in dominant (KCNJ11: OR, 2.07; 95% CI, 1.30-3.27; p - 0.001; KCNQ1: OR, 2.33; 95% CI, 1.46-3.70; p - 0.0003) and codominant models (KCNJ11: OR, 1.76; 95% CI, 1.09-2.84; p - 0.020; KCNQ1: OR, 1.85; 95% CI, 1.16-2.95; p - 0.009). We also compared clinicopathological characteristics between cases and control and observed a significant difference in all the parameters except HDL, gender, and family history. In this study, clinicopathological data with a carrier of a variant allele of both KCNJ11 and KCNQ1 genes were also analysed, and a significant association was found between the carrier of a variant allele with gender and PPG in KCNJ11 and with triglyceride in KCNQ1. We confirm the significant association of KCNJ11 (rs5210) and KCNQ1 (rs2237895) gene polymorphism with T2DM, indicating the role of these variants in developing risk for T2DM in Indian population.

Role of FTO and MC4R Polymorphisms in Escalating Obesity and Their Indirect Association With Risk of T2D in Indian Population.

INTRODUCTION: Obesity plays a pivotal role in the development of metabolic syndrome-excessive body fat, spikes in blood glucose levels and hypertension-and ultimately leads to cardiovascular diseases and type 2 diabetes (T2D), if left unattended. The present study aimed to investigate the associated risk of T2D with obesity risk alleles of fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes. METHODS: The study includes 400 subjects (300 T2D diabetic cases and 100 healthy controls). Genetic analysis was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The findings of the study show no significant increase in odds of diabetes associated with the prevalence of FTO and MC4R minor alleles. Rare allele frequencies for "A" of FTO rs9939609 were 0.34 and 0.30 in cases and controls, respectively. Rare allele frequencies for A of MC4R rs12970134 were found to be more common in controls (0.45) than cases (0.41), but the difference was insignificant (p 0.246); however, an increase in body weight with the presence of allele "A" of the FTO gene (p value < 0.001) was found, indicating indirect involvement in the development of T2D. In addition, these were also correlated with the demographic/lifestyle and clinico-pathological parameters between T2D cases and controls. We found that T2D patients with a history of smoking and high consumption of alcohol, fast foods and sweetened beverages are at high risk of T2D compared to healthy controls (p < 0.01*). CONCLUSION: The present study concludes that there is no direct association of rs9939609 of the FTO gene with the occurrence of diabetes in the Indian population, but its role in T2D development cannot be overlooked altogether. Furthermore, we conclude that the rs9939609 of FTO carries a potential risk of obesity and because of this FTO rs9939609 T > A is widely considered an obesity-associated allele/single-nucleotide polymorphism (SNP).

Association of Her-2 Expression and Clinicopathological Parameters in Colorectal Carcinoma in Indian Population.

BACKGROUND: Human epidermal growth factor receptor 2 (HER-2) is an oncogenic gene and a well-established therapeutic target in several cancers including breast and ovary. AIM: The present study aimed to compare HER-2 expression status with histological grades as well as Clinicopathological parameters including age, bleeding per rectum, pain/burning sensation in defecation and exercise. METHODS: Her-2 status was assessed by immunohistochemistry (IHC). RESULTS: Results of the study shows that 40.96% patients were Her-2 positive for expression and a statistically significant difference (p-value = 0.004) was observed in histological grades where most of the cases were of grade II. We also observed a significant difference in histological grades with gender (p-value = 0.04), as well as in both the age groups ≤ 55 years and > 55 years (p-value = < 0.0001). Patients with the bleeding rectum and pain/burning sensation in defecation had grade II/III tumours (93.4%, 88.7%) respectively. A significant association was observed between bleeding per rectum and pain/burning sensation in defecation. About 95% of patients with pain/burning sensation in defecation had bleeding per rectum. CONCLUSION: To conclude, Her-2 can be a potential prognostic marker in CRC. The role of age, tumour grade and bleeding per rectum/burning sensation in defecation are of significant worth. Thus, CRC cases of high grades can be screened for HER-2/neu positivity so that they can be subjected to mAb-based individualised therapy.

CRP Gene Polymorphism and Their Risk Association With Type 2 Diabetes Mellitus.

BACKGROUND: C-reactive protein (CRP) is an inflammatory marker associated with T2DM, obesity, insulin resistance, and cardiovascular disease. AIM: The present study evaluates the association of CRP +1059 G/C polymorphism of the CRP gene in 100 T2D cases and 100 healthy controls. METHODS: Present study was done by allele specific PCR method to study the CRP gene polymorphism in study subjects. RESULTS: Study found that CRP (+1059 G/C) genotype distribution among case and controls was found to be significant (p=0.001), Higher CRP C allele frequency (0.16) was observed compared to controls (0.04). CRP +1059 GC and CC had 2.72 (1.12-6.61), 20.56 (1.16-362.1) risk for T2D. It has been observed, HTN, Obesity, Smoking and alcoholism was found to be associated with increased risk of T2D, and a significant difference was observed in biochemical parameters. CONCLUSION: Study concluded that CRP gene polymorphism was found to be associated with risk of Type 2 Diabetes and risk was linked with heterozygosity and mutant homozygosity. Hypertension, Obesity, Smoking and alcoholism increases the risk of occurrence of Type 2 Diabetes.

Frequency of I655V SNP of HER-2/neu in colorectal cancer: a study from India.

The present study was conducted to determine the prognostic significance of I655V SNP (rs1136201) is a genetic one in HER-2 oncoprotein in cases of colorectal cancer (CRC). We conducted a case-control study analysing 83 subjects (naïve primary CRC cases) who underwent CRC biopsy/colectomy and included 57 healthy control subjects. Analysis of HER-2 polymorphism was done by PCR-RFLP technique. The mean age was found to be 55.9 years; median age was 56 years and mode age was 54 years with a range of 43 (30-73). Males constitute 63 (75.9%) and females constitute 20 (24.1%) of patient population. According to gradewise distribution, 12 (14.45%) patients were of Grade I, 53 (63.85%) of Grade II, and 18 (21.68%) were of Grade III. We found out that out of 83 patients, 52 (62.65%) were of homozygous wild type (A/A; Ile/Ile); 27 (32.53%) were of heterozygous type (A/G; Ile/Val) and 4 (4.81%) were of homozygous mutant type (G/G; Val/Val). Allelic frequency of Ile (A) was found out to be 0.79 and that of Val (G) is 0.21 and were not significantly different from the healthy control population. Fischer's exact p value obtained was 0.86.