Spinocerebellar Ataxias in India: Three­year Molecular Data from a Central Reference Laboratory.

INTRODUCTION: There is a great deal of heterogeneity, both phenotypically and genotypically among the autosomal dominant cerebellar ataxias (ADCA). Their prevalence also varies in different populations. Trinucleotide repeat expansions (CTG/CAG) have been shown predominantly to cause a number of ADCAs. AIM: The present study describes the frequency of spinocerebellar ataxias (SCA) and the CAG repeat sizes among the different regions of India. SETTINGS AND DESIGN: Molecular data from our central reference laboratory were retrospectively analyzed for SCAs 1, 2, 3, 6, 7, 10, 12, 17 and DRPLA. Correlation between age at diagnosis and the CAG repeats of the expanded and the normal alleles were tested with the Spearman correlation test. RESULTS: The presence of SCAs vary according to geographical regions and ethnicities; SCA 12 was detected with the highest frequency (229/901), but was restricted to a specific ethnic population, followed by SCA 2 with a positivity of 12% (101/845). SCA 3 previously known as Machado-Joseph Disease had a prevalence of 4.05% (32/789), whereas SCA 1 was diagnosed in 30/773 (3.88%). No positivity was seen for SCA 10 from the 103 samples tested and for SCA 17 from the 131 samples tested either as a part of an extended panel or stand-alone. CONCLUSION: In this report, we are able to expand the portrait of SCAs in India by presenting the largest ever molecular data from a central reference laboratory.

Variant on 9p21 is strongly associated with coronary artery disease but lacks association with myocardial infarction and disease severity in a population in Western India.

BACKGROUND AND AIMS: Coronary artery disease (CAD) is the leading cause of death worldwide, especially so in Indians. Recently, genome-wide studies have implicated SNPs in the 58 kb region of chromosome 9p21 to be associated with CAD. In the current study we evaluated the association of single nucleotide polymorphism (SNP) rs10757278 at the 9p21 locus with CAD in a population from Western India. METHODS: Genotyping for rs10757278 A/G was done by direct sequencing in 215 cases with confirmed CAD and 150 controls. RESULTS: A significantly higher frequency of the G allele was seen in cases as compared to controls (0.64 vs. 0.53). In the current study the G allele showed association with risk of CAD (OR 1.832 per G allele 95% 1.035-3.242, P 0.042; OR 2.452 GG vs. AA 95% 1.358-4.4431, P 0.004). Addition of the 9p21 allele to Framingham risk score (FRS) resulted in a shift of 17% of individuals from the low-risk category to the intermediate-low (>5-<10% 10-year risk) and 7% from intermediate-low to intermediate-high (>10-<20% 10-year risk) categories. CONCLUSIONS: The rs10757278 G variant at the 9p21 locus is significantly associated with the risk of CAD in our population of Western India, similar to the observed trend in other populations; however, the association is much stronger in the present cohort and, considering the high propensity of Indians to develop CAD, it is an important marker even in terms of risk classification.

Genetic variants at the APOE, lipoprotein lipase (LpL), cholesteryl ester transfer protein (CETP), and endothelial nitric oxide (eNOS) genes and coronary artery disease (CAD): CETP Taq1 B2B2 associates with lower risk of CAD in Asian Indians.

Coronary artery disease (CAD) arises due to a complex interplay between the environment and genetic factors. Alterations in many of the biomarkers such as lipids and lipoprotein levels are characteristic of CAD. The phenotypes themselves have genetic determinants, and many single-nucleotide polymorphisms (SNPs) have been identified which influence them. The current study aims to evaluate the effect of six common polymorphisms at four loci, lipoprotein lipase (D9N, N291S, S447X), apolipoprotein E (APOE), cholesteryl ester transfer protein (C277T), and endothelial nitric oxide synthase (E298D), on lipid and lipoprotein levels and its association with CAD. Genotyping for the SNPs was done in 240 Indians of which 90 had proven CAD. The other 150 were clinically free from CAD and acted as controls. Relation of genetic variants, clinical history, and biochemical parameters with CAD were analyzed by multiple regression analysis. The frequency of the B2 allele in the CETP gene was significantly lower in cases than in controls (0.40 vs 0.49, P = 0.042). Significant association of CETP Taq1B SNP was seen with total cholesterol and low density lipoprotein cholesterol. Multivariate analysis accounting for clinical and metabolic predictors of CAD showed smoking to be a significant risk factor (odds ratio (OR) 4.347, 95% confidence interval (CI) 1.888-10.012, P = 0.001) and the CETP B2 variant imparting atheroprotection (OR 0.312, 95% CI 0.116-0.841, P = 0.021) possibly through a favorable lipid profile. None of the other SNPs were associated with the risk of CAD.