Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

Changes in natural OSL sensitivity during single aliquot regeneration procedure and their implications for equivalent dose determination

Measurement of low temperature (90°C-120°C) Thermoluminescence (TL) sensitivity of natural quartz samples subjected to pre-heating and optical stimulation indicate that significant sensitivity changes can occur during measurement of the natural Optically Stimulated Luminescence (OSL). During the measurement of natural signal, the luminescence sensitivity of samples can change by 40%. The sensitivity changes both during the initial preheat and the measurement of natural OSL. The currently used version of Single Aliquot Regeneration (SAR) protocol measures and corrects for the sensitivity changes after preheat and readout of natural OSL. However, it does not take into account the changes in sensitivity during the readout of the natural signal. We therefore developed a correction procedure so that both the natural and the regenerated OSL intensities can be measured and plotted with the same sensitivity and suggest that in the absence of such a correction, a considerable fraction of the SAR based ages could have systematic errors. The correction for the sensitivity is based on the use of sensitivity of 110°C TL quartz peak, which is correlated to OSL signal (Murray and Roberts, 1998). The use of 110°C peak provides a reasonable measure of the changes in OSL sensitivity of quartz. A modified Natural Sensitivity Corrected-SAR (NSC-SAR) procedure, that comprises the measurement of, 1) the TL intensity of 110°C peak for a test dose on sample as received (i.e. natural sample) and, 2) the sensitivity of the 110°C peak of the same sample after the preheat and read out of the natural OSL, is proposed. This ratio, termed as Natural Correction Factor (NCF), then provides a way to correct for sensitivity changes. Results on samples from diverse depositional environments indicated that the NSC-SAR consistently (without exception) provided improved distribution in paleodoses i.e. a lower scatter compared to the standard SAR protocol. In addition, the use of this protocol also resolved anomalous cases where the intensity of natural OSL was significantly above the saturation intensity of the regenerated OSL. Implicitly, this study implies a caution on the use of palaeodoses obtained from single grains as such a correction is not possible in the currently used automated single grain OSL measurement systems. The only way now on will be to analyze aliquots with only a grain on them

Statistical analysis of differential gene expression profile for colon cancer

396-403To analyze differentially expressed genes in colon cancer, we compared expression profiles of colorectal cancer cells from normal colonic cells using data of DNA microarray consisting of 6584 human genes. Each probe set on the array consisted of EST (expressed sequence tag) sequence of 20 feature pairs of 25 bp sequence. The data set comprised of 61 samples, divided into two groups of 40 samples for tumor cells (Group 1) and 21 samples for normal cells (Group 2). In order to do background adjustments for the negative expression values, the data was transformed into log base 2 and estimation of missing values was performed by K-nearest neighbor method, followed by normalization using ‘minimum mean ratio’ among arrays. The basic statistics used for the significance analysis was J5 test, which was computed for each probe and for each contrast with a threshold value of 4.0 and mean as the measure of central tendency. The differentially expressed genes were expressed at high frequency in tumour samples. The Naive Bayes Classifier Algorithm was used to test defined classification of samples of genes. Correlation distance was measured with the help of Pearson’s correlation distance. On the basis of J5 test scores, top 5 upregulated genes, viz., vasopressin-neurophysin 2-copeptin preproprotein, cytochrome, P450 2A7 isoform, major centromere autoantigen B, myelin associated glycoprotein and bone morphogenetic protein 1 isoform 3 precursor, were selected for further analysis. The above said genes have not yet been reported to be differentially overexpressed in colon cancer cells, while their overexpression was reported in other cancers, such as, lung and breast cancer, etc. These genes can be used for prediction and analyses of the gene products, which will help in designing new diagnostic and treatment strategies for the colon cancer

Establishing reference ranges and normal values for coagulation screening in healthy Indian male volunteers enrolled for a longitudinal study

Background: The study was designed for establishing reference ranges and normal values for coagulation screening in healthy Indian male volunteers. At present, there are no standard parameters established for coagulation screening assays of Indian population. The parameters used as a reference in the coagulation assays are of Western origin. We know that ethnicity of the western population is different from the Indian population which may result in a different set of reference ranges of the coagulation assay. It is necessary to determine the mean normal values for the coagulation assay, namely prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen in an Indian population. The aim of the study was to establish the reference ranges of coagulation assays for all future experiments on the cohort. Methods: Six hundred healthy male volunteers were sampled and underwent coagulation testing at a seven hundred-bedded hospital at Jammu (Jammu). Fresh normal pool plasma (FNPP) was prepared concurrently and investigated (n = 50 volunteers). In the study population, the arithmetic means of the coagulation assay were as follows: PT: 13.00 s, APTT: 34 s, TT: 17.3 s, and fibrinogen: 298 mg/dl (19 s), and in the FNPP, it was 12.8 s, 33.2 s, 17 s, and 298 mg/dl (19 s), respectively. Results: The reference range of coagulation screening in our study was established as the following values: PT: 10.7–15.3 s, APTT: 26.8–41.2 s, TT: 12.8–21.7 s, and fibrinogen: 223–372 mg/dl. This study has set a reference range of normal values for coagulation assay screening in longitudinal studies where these tests were repeated on the same set of individuals at six-month interval for the subsequent 3 years. Conclusion: We see no effect of age on Coagulation cascade in our study. Overall mean values resembled with various age groups in coagulation cascade. These parameters of Coagulation cascade set a standard for high altitude studies where these tests are in normal procedure