Targeted exome sequencing in South Indian patients with Familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD). OBJECTIVES: In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing. METHODS: 54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC). Targeted exome sequencing was performed using 23 gene panel associated with lipid metabolism. RESULTS: All subjects showed the presence of family history of CAD, 38(70%) patients had corneal arcus whereas only 06(11%) subjects had xanthomas. As per the DLCNC, definite, probable, possible and unlikely FH were 48%, 30%, 11% and 11% respectively. Mutations were observed in 12 of the 23 gene panel with CETP, APOA5, EPHX2 and SREBP2 genes were identified for the first time in Indian FH patients. All 19 mutations including a novel frame-shift mutation in LDLR gene were reported for the first time in Indian FH patients. These mutations were identified in 28(52%) subjects and interestingly ∼73% of the clinically identified FH patients didn't harbour mutations in FH classical genes (LDLR, ApoB, PCSK9). CONCLUSION: This is the first study in the South Indian FH patients to perform targeted exome sequencing. Absence of mutations in the FH classical genes strongly indicates the polygenic nature of FH, further underscoring the importance of targeted exome sequencing for identifying mutations in genetically diverse Indian population.

Geographical variation in the clinical presentation of endomyocardial fibrosis in India?

OBJECTIVES: To compare the clinical presentation, clinical profile and survival of two groups of endomyocardial fibrosis patients. METHODS: The study was a prospective cohort study, or a prospective case series, comparing all consecutive echocardiographically proven patients with endomyocardial fibrosis seen in Medical College Trivandrum with the patients seen in Medical College Hospital, Alappuzha(Alleppey) (or TD Medical College). In all patients the clinical details like age, sex, type of endomyocardial fibrosis, the presence of anaemia, eosinophilia, neutrophilia and type of rhythm(Sinus or atrial fibrillation) etc were compared by both simple X2 and by Kaplan Meier survival curves. RESULTS: The mean age and the sex distribution was same in both places Briefly the incidence of biventricular endomyocardial fibrosis was more from Trivandrum than Alleppey, 64.9% vs 14.3% (p<0.0.001), the incidence of atrial fibrillation was more in Trivandrum 44.2% vs 16.3%. (p<0.001)The overall survival of Trivandrum patients was poorer (p<0.0001). The six year survival was 61% in the Trivandrum population whereas it was 91.5% in the Alleppey population. CONCLUSIONS: These differences may have been due to the better nutrition of the Alleppey patients due to a higher exposure to fish compared to the Trivandrum population. Better nutrition would protect against Magnesium deficiency and prevent the absorption of Cerium in the patients from Alleppey, compared to those from Trivandrum.

Sex Differences in the Presentation, Diagnosis, and Management of Acute Coronary Syndromes: Findings From the Kerala-India ACS Registry.

BACKGROUND: Previous literature from high-income countries has repeatedly shown sex differences in the presentation, diagnosis, and management of acute coronary syndromes (ACS), with women having atypical presentations and undergoing less aggressive diagnostic and therapeutic measures. However, much less data exist evaluating sex differences in ACS in India. OBJECTIVES: This study sought to evaluate sex differences in the diagnosis, management, and treatment of patients with ACS in Kerala, India. METHODS: The Kerala ACS Registry collected data from 25,748 consecutive ACS admissions (19,923 men and 5,825 women) from 125 hospitals in the Indian state of Kerala from 2007 to 2009. This study evaluated the association between sex differences in presentation, in-hospital management, and discharge care with in-hospital mortality and in-hospital major adverse cardiovascular events (defined as death, reinfarction, stroke, heart failure, or cardiogenic shock). RESULTS: Women with ACS were older than men with ACS (64 vs. 59, p < 0.001) and were more likely to have a history of previous myocardial infarction (16% vs. 14%, p < 0.001). Inpatient diagnostics and management and discharge care were similar between sexes. No significant differences between men and women in the outcome of death (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 0.80 to 1.38) or in the composite outcome of death, reinfarction, stroke, heart failure, or cardiogenic shock (OR: 0.99, 95% CI: 0.79 to 1.25) were seen after adjustment for possible confounding factors. CONCLUSIONS: In Kerala, even though women with ACS were older and more likely to have previous myocardial infarction, there were no significant differences in in-hospital and discharge management, in-hospital mortality, or major adverse cardiovascular events between sexes. Whether these results apply to other parts of India or acute presentations of other chronic diseases in low- and middle-income countries warrants further study.

An uncommon picture of endomyocardial fibrosis: no embolism yet.

We present here a review of the various gradings of endomyocardial fibrosis from autopsy (Shaper's types). Echocardiography accurately delineates the extent of fibrosis of either the right or left ventricle and we have illustrated a typical classical case. We have images of the same patient from 2010, 2011 and 2012 and so we use this to illustrate the echocardiographic gradings.