LDL-R AvaII and NcoI Polymorphisms: An Indirect Risk Factor for Coronary Heart Disease Among a Mendelian Population of Delhi, India

Sinha, Ekata; Walia, Gagandeep Kaur; Gupta, Budh Prakash; Ghosh, Pradeep; Saraswathy, Kallur Nava

doi:10.1007/s10528-010-9361-0

Cited by 4 publications

(1 citation statement)

References 19 publications

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“…However, at least one of these genes, ApoA5 , has been well characterized as associated with triglyceride levels, ( Charlton-Menys and Durrington 2005 ). In humans, a mutation in ApoA5 , also called the Delhi gene, is linked to extremely elevated triglyceride levels and increased risk of cardiovascular disease ( Sinha et al 2010 ; Ramakrishnan et al 2011 ). Hepatic lipase, encoded by the Lipc gene, hydrolyzes triglycerides and phospholipids in lipoprotein particles and is therefore also likely to be functionally associated with heart disease.…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Genetic Mapping in the Diversity Outbred Mouse Population Identifies Apobec1 as a Candidate Gene for Atherosclerosis

Smallwood

Gatti

Quizon

et al. 2014

G3 Genes|Genomes|Genetics

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Inbred mice exhibit strain-specific variation in susceptibility to atherosclerosis and dyslipidemia that renders them useful in dissecting the genetic architecture of these complex diseases. Traditional quantitative trait locus (QTL) mapping studies using inbred strains often identify large genomic regions, containing many genes, due to limited recombination and/or sample size. This hampers candidate gene identification and translation of these results into possible risk factors and therapeutic targets. An alternative approach is the use of multiparental outbred lines for genetic mapping, such as the Diversity Outbred (DO) mouse panel, which can be more informative than traditional two-parent crosses and can aid in the identification of causal genes and variants associated with QTL. We fed 292 female DO mice either a high-fat, cholesterol-containing (HFCA) diet, to induce atherosclerosis, or a low-fat, high-protein diet for 18 wk and measured plasma lipid levels before and after diet treatment. We measured markers of atherosclerosis in the mice fed the HFCA diet. The mice were genotyped on a medium-density single-nucleotide polymorphism array and founder haplotypes were reconstructed using a hidden Markov model. The reconstructed haplotypes were then used to perform linkage mapping of atherosclerotic lesion size as well as plasma total cholesterol, triglycerides, insulin, and glucose. Among our highly significant QTL we detected a ~100 kb QTL interval for atherosclerosis on Chromosome 6, as well as a 1.4 Mb QTL interval on Chromosome 9 for triglyceride levels at baseline and a coincident 22.2 Mb QTL interval on Chromosome 9 for total cholesterol after dietary treatment. One candidate gene within the Chromosome 6 peak region associated with atherosclerosis is Apobec1, the apolipoprotein B (ApoB) mRNA-editing enzyme, which plays a role in the regulation of ApoB, a critical component of low-density lipoprotein, by editing ApoB mRNA. This study demonstrates the value of the DO population to improve mapping resolution and to aid in the identification of potential therapeutic targets for cardiovascular disease. Using a DO mouse population fed an HFCA diet, we were able to identify an A/J-specific isoform of Apobec1 that contributes to atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

High-Resolution Genetic Mapping in the Diversity Outbred Mouse Population Identifies Apobec1 as a Candidate Gene for Atherosclerosis

Smallwood

Gatti

Quizon

et al. 2014

G3 Genes|Genomes|Genetics

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APOE, MTHFR, LDLR and ACE Polymorphisms Among Angami and Lotha Naga Populations of Nagaland, India

et al. 2011

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Several common polymorphisms in the ApoE, ACE, MTHFR and LDLR genes have been implicated in the pathogenesis of common complex diseases across world populations. This study investigates the prevalence of five known and clinically important common polymorphisms in Angami and Lotha Naga populations. A total of 112 unrelated healthy volunteers (52 Lotha Nagas and 60 Angami Nagas) participated in the study. All the five genes were found to be polymorphic in the studied populations. The Lotha Nagas displayed higher mutant allele frequencies than the Angami Nagas except for the T allele frequency of the AvaII polymorphism of the LDLR gene, though chi square did not reveal any significant population differences by genotypes. In view of the relatively high mutant allele frequencies in both the populations, they are likely to be at a high risk of developing various complex diseases as they shift from an active and rigorous lifestyle to a more sedentary one.

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Linkage Disequilibrium between LDLR rs688 and AvaII Genes and its Significant Association with Ischemic Stroke

Chen¹,

Cai²,

Zhang³

et al. 2023

J. Integr. Neurosci.

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Background: To analyze the polymorphism distribution of low density lipoprotein receptor rs688, AvaII, NcoI gene in ischemic stroke, and explore the linkage disequilibrium among them. The correlation between the linkage disequilibrium and ischemic stroke was further analyzed. Methods: The levels of serum lipid (triglyceride, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B) and rs688, AvaII, NcoI polymorphism of low density lipoprotein receptor gene were tested in patients with ischemic stroke (n = 140), healthy control (n = 129) and patients with other cerebrovascular diseases (n = 122). Chi-square test was used to compare the gene frequency and allele frequency of each group. Both the linkage disequilibrium of the three genes and the alleles correlated with ischemic stroke were analyzed. The correlation of linkage disequilibrium gene and ischemic stroke was analyzed with logistic binary regression. Results: In the ischemic stroke group, significant difference was observed in frequencies and allelic frequencies of low density lipoprotein receptor (LDLR) rs688 and AvaII. No difference of NcoI was found. Linkage disequilibrium was found for rs688 and AvaII (D’ = 0.927, R2 = 0.509). Allelic genes correlate with ischemic stroke included T of rs688 (X2 = 46.105, p < 0.001) and C of AvaII (X2 = 20.436, p < 0.001). Conclusions: Linkage disequilibrium existed between LDLR rs688 and AvaII genes. With the wild type gene (WT) (rs688/AvaII: CC/TT) as reference, rs688/AvaII: CT/TC, CT/CC and TT/CC increased the risk of ischemic stroke, which might be a genetic marker used for the screen of high-risk population contributing to the prevention of the disease.

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LDL-R AvaII and NcoI Polymorphisms: An Indirect Risk Factor for Coronary Heart Disease Among a Mendelian Population of Delhi, India

Cited by 4 publications

References 19 publications

High-Resolution Genetic Mapping in the Diversity Outbred Mouse Population Identifies Apobec1 as a Candidate Gene for Atherosclerosis

High-Resolution Genetic Mapping in the Diversity Outbred Mouse Population Identifies Apobec1 as a Candidate Gene for Atherosclerosis

APOE, MTHFR, LDLR and ACE Polymorphisms Among Angami and Lotha Naga Populations of Nagaland, India

Linkage Disequilibrium between LDLR rs688 and AvaII Genes and its Significant Association with Ischemic Stroke

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