Genetic variants of chromosome 9p21.3 region associated with coronary artery disease and premature coronary artery disease in an Asian Indian population

Introduction Asian Indians have a propensity for premature, severe, and diffuse coronary artery disease (CAD). Several single-nucleotide polymorphisms (SNPs) in the ‘core CAD’ region of the chromosomal region 9p21.3 are known to be strongly associated with CAD. Objectives We aimed to study SNPs in the 9p21.3 region associated with CAD and premature CAD and identify their association with demographic and clinical characteristics in an Asian Indian population. Methods SNP genotyping was performed for 30 SNPs of the 9p21.3 region using MassARRAY® technology. Along with demographic and SNP data analysis, we also performed multivariate logistic regression analysis and multifactor dimensionality reduction analysis to study SNP–SNP and SNP–demographic/clinical variable interactions. Results Our results suggest that females are at a higher risk of premature CAD. We found that SNPs rs1333045 (CC), rs16905599 (AA), rs2383206 (GG), rs2383208 (AG), and rs4977574 (GG) were significantly associated with premature CAD. When adjusted for covariates/confounders, we found that rs2383206 showed the strongest risk association with CAD followed by rs16905599 and rs2383208. Further, SNPs rs1333049 (CC) and rs4977574 (GG) were found to be exclusively associated with premature CAD cases, suggesting their potential as genetic markers for premature CAD in the local population. Upon gender-based stratification, it was found that rs10757272 (TT and TC) is significantly associated with eightfold to ninefold CAD risk specifically among females. SNP rs7865618 (GG) is significantly associated with more than 2.5-fold CAD risk specifically among males. Conclusion Our study suggests that SNPs at the 9p21 risk locus may be used to generate a reliable genetic risk score along with markers at other loci.

Influence of disc area on retinal nerve fiber layer thickness measurement by spectral domain optical coherence tomography.

Background: To examine the eff ect of optic disc area on peripapillary RNFLT (retinal nerve fi ber layer thickness) measurement at circle diameter of 3.4 mm around optic nerve head using spectral OCT/SLO (Optical coherence tomography/scanning laser ophthalmoscope). Materials and Methods: In this prospective, cross sectional study, one hundred and two eyes of 102 normal subjects underwent RNFLT and disc area measurement using spectral OCT/SLO. Based on disc area, subjects were divided into three groups i.e., <3 mm2 (32 eyes), 3-4 mm2 (36 eyes) and >4 mm2 (34 eyes). The eff ect of disc area on RNFLT parameters was analyzed using linear regression analysis. Results: The mean and quadrant RNFLT did not show signifi cant correlation with disc area in subjects with disc area of <4 mm2, however in eyes with disc area >4 mm2, average RNFLT, superior and temporal quadrant RNFLT showed negative correlation with disc area, which was statistically signifi cant (P = 0.004, P = 0.005 and P = 0.002, respectively) Conclusion: In healthy eyes of disc area <4 mm2, disc size does not appear to aff ect peripapillary RNFLT measurement by spectral OCT/SLO. Average, superior and temporal quadrant RNFLT measurements were inversely proportional to disc area in eyes with disc area >4 mm2. Hence, RNFLT measurement by OCT in eyes with optic disc area of >4 mm2 should be interpreted carefully.

Quantification of retinal nerve fiber layer thickness using spectral domain optical coherence tomography in normal Indian population.

The purpose of this study was to measure peripapillary retinal nerve fiber layer thickness (RNFLT) using spectral domain optical coherence tomography (SD-OCT) in normal Indian eyes, for which, 210 normal volunteers were recruited. One eye of each subject underwent RNFL scanning at 3.4 mm circle diameter around optic nerve using SD OCT. The data were analyzed to determine RNFLT in the sample population and its variation with age and gender. The average peripapillary RNFLT was 114.03 ± 9.59 μm. There was no effect of gender on RNFLT parameters. Age had significant negative correlation with average (P = 0.005), superior (P = 0.04), temporal (P = 0.049), and nasal quadrants (P = 0.01) RNFLT. Inferior quadrant RNFLT also had a negative correlation with age, but it was not statistically significant (P = 0.15).

Role of proteases and antiprotease in the etiology of chronic pancreatitis

Chronic pancreatitis [CP] is the progressive and irreversible destruction of the pancreas characterized by the permanent loss of endocrine and exocrine function. Trypsin, the most important digestive enzyme plays a central role in the regulation of all other digestive enzymes. Chymotrypsin, an endopeptidase hydrolyzes peptides at amino acids with aromatic side chains. Alpha-1-antitrypsin is a principal antiprotease which protects the mucosal tissue from the proteolytic effects of trypsin and chymotrypsin by the formation of molar complexes. The present study is aimed at examining the role of proteases [trypsin and chymotrypsin] and anti-protease [alpha1-anti-trypsin] in the etiopathogenesis of chronic pancreatitis. A total of 90 CP patients and 110 age and sex matched controls were considered for the study. Serum trypsin, chymotrypsin and alpha1-anti-trypsin levels were determined prospectively in CP patients and compared to healthy controls as described previously. The mean activity of trypsin were found to be increased in CP patients [X +/- SD = 0.82 +/- 0.838] in comparison to normal control group [X +/- SD = 0.55 +/- 0.328], [P = 0.001]. Chymotrypsin activity were also found to be elevated in CP patients [X +/- SD = 0.63 +/- 0.278] in comparison to control group [X +/- SD = 0.39 +/- 0.295], [P = 0.0001]. The mean alpha-1-anti-trypsin activity were found to be lowered in CP patients [X +/- SD = 0.42 +/- 0.494] in comparison to control group [X +/- SD = 0.67 +/- 0.465], with the variation being significant [P = 0.0003]. The findings suggest an imbalance in the synthesis and degradation of proteolytic enzymes and antiprotease indicating an altered aggressive and defensive role in the pathogenesis of chronic pancreatitis

Ability of spectral domain optical coherence tomography peripapillary retinal nerve fiber layer thickness measurements to identify early glaucoma.

Purpose: To evaluate the ability of spectral domain optical coherence tomography (OCT) peripapillary retinal nerve fiber layer thickness (RNFLT) parameters to distinguish normal eyes from those with early glaucoma in Asian Indian eyes. Design: Observational cross-sectional study. Materials and Methods: One hundred and seventy eight eyes (83 glaucoma patients and 95 age matched healthy subjects) of subjects more than 40 years of age were included in the study. All subjects underwent RNFLT measurement with spectral OCT/ scanning laser ophthalmoscope (SLO) after dilatation. Sensitivity, specificity and area under the receiving operating characteristic curve (AROC) were calculated for various OCT peripapillary RNFL parameters. Results: The mean RNFLT in healthy subjects and patients with early glaucoma were 105.7 ± 5.1 μm and 90.7 ± 7.5 μm, respectively. The largest AROC was found for 12 o’clock- hour (0.98), average (0.96) and superior quadrant RNFLT (0.9). When target specificity was set at ≥ 90% and ≥ 80%, the parameters with highest sensitivity were 12 o’clock -hour (91.6%), average RNFLT (85.3%) and 12 o’ clock- hour (96.8 %), average RNFLT (94.7%) respectively. Conclusion: Our study showed good ability of spectral OCT/ SLO to differentiate normal eyes from patients with early glaucoma and hence it may serve as an useful adjunct for early diagnosis of glaucoma.

Association of hypertension with risk factors & hypertension related behaviour among the aboriginal Nicobarese tribe living in Car Nicobar Island, India

Background & objectives: There are no composite estimates on prevalence of hypertension among indigenous tribes in India. The present study was carried out to estimate the prevalence of hypertension, its association with determinants, and to assess the hypertension related behaviour of the Nicobarese aborigines. Methods: This cross-sectional survey was carried during 2007 and 2009. Subjects were chosen by two stage design. Total 975 subjects of 1270 (response rate of 76.8%) were investigated (M: 43.5%; F: 56.5%). The data were collected by history, clinical examination (blood pressure), and examination (weight and height). The association of hypertension with age, education, tobacco, alcohol consumption and their dependency status (KF score, QF value, and AUDIT score) and nutritional status was estimated by bivariate regression analysis; the increasing trend in the prevalence of hypertension with increasing age and decreasing educational status was analysed by χ2 for linear trend. Significant variables in bivariate regression analysis (age, education, alcohol consumption status, and nutritional status) were subjected to multiple logistic regression analysis (MLR). Results: The prevalence of hypertension was 50.5 per cent [95% CI 46.1-54.9 (M: 50.7%; F: 50.3%)]. The prevalence of tobacco, alcohol consumption, and overweight/obesity was 88, 54, and 37 per cent respectively. The bivariate analysis has shown association between hypertension and age, education subcategories, alcohol consumption, and overweight/obesity (P<0.05). The increasing trend in the prevalence of hypertension with increasing age (χ2 for linear trend=95.88, P< 0.001) and decreasing educational status (χ2 for linear trend=25.55, P< 0.001) was statistically significant. MLR analysis revealed a significant association between hypertension and various age categories and overweight/obesity. Interpretation & conclusions: The findings of the present study highlight high prevalence of hypertension among Nicobarese aborigenes.

Optic disc topography in normal Indian eyes using spectral domain optical coherence tomography.

Purpose: The aim was to study optic nerve head (ONH) parameters in normal Indian eyes using spectral domain optical coherence tomography (OCT)/scanning laser ophthamoscope (SLO). Materials and Methods: One hundred and fifty-seven eyes of 157 normal subjects of various age groups underwent ONH imaging with spectral OCT/SLO and the parameters obtained were correlated with disc size. The effect of age, gender, and refractive error on various ONH parameters were also studied. Results: The mean optic disc area was 3.36 ± 0.64 mm2 (range, 2.13–5.08 mm2), mean rim area was 2.49 ± 0.58 mm2 (range, 1.20–3.62 mm2), and mean cup area was 1.10 ± 0.75 mm2 (range, 0–3.07 mm2). The disc area showed significant positive correlation with the rim area, cup area, horizontal cup disc ratio, vertical cup disc ratio, cup disc area ratio, mean cup depth, and maximum cup depth (P < 0.001). Neither gender nor refractive error showed any significant difference in various ONH parameters. ONH parameters did not show significant change with age except for rim area which declined with the advancing age (r = –0.25, P < 0.001). Conclusions: The quantitative measurement of ONH topography obtained with this study provides a normative database for an Indian population with spectral OCT/SLO. As optic disc area influences ONH topography, disc size should to be considered when evaluating optic disc for progressive optic neuropathies such as glaucoma.