Additional file 2: Table S2. of Prevalence, awareness, treatment and control of dyslipidemia in older persons in urban and rural population in the Astana region, Kazakhstan

Factors associated with serum cholesterols in Astana region, Kazakhstan, OR (95% CI). (DOC 92 kb

<i>RYR2</i> Sequencing Reveals Novel Missense Mutations in a Kazakh Idiopathic Ventricular Tachycardia Study Cohort

<div><p>Channelopathies, caused by disturbed potassium or calcium ion management in cardiac myocytes are a major cause of heart failure and sudden cardiac death worldwide. The human ryanodine receptor 2 (RYR2) is one of the key players tightly regulating calcium efflux from the sarcoplasmic reticulum to the cytosol and found frequently mutated (<60%) in context of catecholaminergic polymorphic ventricular tachycardia (CPVT1). We tested 35 Kazakhstani patients with episodes of ventricular arrhythmia, two of those with classical CPVT characteristics and 33 patients with monomorphic idiopathic ventricular arrhythmia, for variants in the hot-spot regions of the <i>RYR2</i> gene. This approach revealed two novel variants; one de-novo <i>RYR2</i> mutation (c13892A>T; p.D4631V) in a CPVT patient and a novel rare variant (c5428G>C; p.V1810L) of uncertain significance in a patient with VT of idiopathic origin which we suggest represents a low-penetrance or susceptibility variant. In addition we identified a known variant previously associated with arrhythmogenic right ventricular dysplasia type2 (ARVD2). Combining sets of prediction scores and reference databases appeared fundamental to predict the pathogenic potential of novel and rare missense variants in populations where genotype data are rare.</p></div

List of nonsynonymous RYR2 single nucleotide variants^*.

<p>*AA: Amino Acid. D: Damaging. VUS: Variant of Unknown Significance. B: Benign. SCD: Sudden Cardiac Death. CD: Cardiac Death.</p

Electropherograms of RYR2 sequences from patients #271 (a), #239 (b), and #444 (c).

<p>Electropherograms of RYR2 sequences from patients #271 (a), #239 (b), and #444 (c).</p

Allele frequencies of common RYR2 single nucleotide polymorphisms in various study populations.

<p>Allele frequencies of common RYR2 single nucleotide polymorphisms in various study populations.</p

Frequency of RYR2 single nucleotide variants.

<p>KazVTSG: Kazakh Ventricular Tachycardia Study Group (n = 35). KazBCSC: Kazakh Breast Cancer Study Cohort (n = 96). KazCG: Kazakh control group (n = 192). HGMD: Human Genome Mutation Database. ESP6500, the 1000Genomes and the 192 KazCG are negative for the observed RYR2 variants. Variant p.V1810L was detected in 1/96 unrelated female breast cancer patient from the KazBCSC.</p

Information on whole mitochondrial genome sequences which used for comparison.

Information on whole mitochondrial genome sequences which used for comparison.</p

Schematic phylogenetic tree for the haplogroup C4a1 mitochondrial genomes.

Note: Alt: Altaian; Bur: Buryat; Uyg: Uyghur; Kir: Kirghiz; Tib: Tibetan.</p

Results from Tajima’s Neutrality Test [33].

Results from Tajima’s Neutrality Test [33].</p

Map of Jetisuu and the sampling sites.

1. Engbekshi Kazak; 2. Talghar; 3. Ile; 4. Almati; 5. Karasay; 6. Jambil; 7. Balkash; 8. Karatal; 9. Köksuu; 10. Taldikorghan; 11. Eskeldi; 12. Kerbulak; 13. Panfilov; 14. Kegen; 15. Rayimbek.</p