scholarly journals Genetic Predisposition to Low-Density Lipoprotein Cholesterol May Increase Risks of Both Individual and Familial Alzheimer's Disease

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiang-Shan Tan ◽  
Meng-Jin Hu ◽  
Yan-Min Yang ◽  
Yue-Jin Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
History Of ◽  
Mr Study

Background: Previous observational studies provided conflicting results on the association between low-density lipoprotein cholesterol (LDL-C) level and the risk of Alzheimer's disease (AD).Objective: We used two-sample Mendelian randomization (MR) study to explore the causal associations between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.Methods: Summary-level genetic data for LDL-C were acquired from results of the UK Biobank GWAS. Corresponding data for paternal, maternal, and family history of AD were obtained from the NHGRI-EBI Catalog of human genome-wide association studies. Data for individual AD were obtained from the MR-Base platform. A two-sample MR study was performed to explore the causal association between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.Results: Genetically predicted LDL-C was positively associated with individual [Odds ratio (OR) = 1.509, 95% confidence interval (CI) = 1.140–1.999; P = 4.0 × 10−3], paternal [OR = 1.109, 95% CI = 1.053–1.168; P = 9.5 × 10−5], maternal [OR = 1.132, 95% CI = 1.070–1.199; P = 2.0 × 10−5], and family history of AD [OR = 1.124, 95% CI = 1.070–1.181; P = 3.7 × 10−6] in inverse variance weighted analysis. After performing weighted median and MR-Egger analysis, consistent results were observed. There was no horizontal pleiotropy in the two-sample MR analysis.Conclusions: High level of LDL-C may increase the risks of both individual and familial AD. Decreasing the LDL-C to a reasonable level may help to reduce the related risk.

Low Density Lipoprotein Cholesterol/Apolipoprotein B-100 Ratio: Interaction of Family History of Premature Atherosclerotic Coronary Artery Disease With Race and Gender in 7 to 11 Year Olds

PEDIATRICS ◽  
1994 ◽  
Vol 94 (4) ◽  
pp. 494-499
Author(s):  
Syed Islam ◽  
Bernard Gutin ◽  
Tina Manos ◽  
Clayton Smith ◽  
Frank Treiber
Keyword(s):  
Family History ◽  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Positive Family History ◽  
Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
White Girls ◽  
History Of ◽  
Artery Disease

Background. In adults, a low density lipoprotein cholesterol (LDL-C)/apolipoprotein B-100 (ApoB) ratio is an indicator of ApoB-enriched small dense LDL, which is associated with premature coronary artery disease (CAD). Since this LDL subclass may be inherited, we investigated whether a low LDL-C/ApoB ratio was associated with a positive family history of premature CAD in young children. Methods. Subjects were 66 children aged 7 to 11 years who were recruited through a school-based family history survey, flyers, and hospital newspaper advertisements. They were divided according to family history and assessed for fatness, blood pressure, lipids, lipoproteins, and apoproteins. Results. Family history interacted with gender such that girls with a positive family history had a lower LDL-C/ApoB ratio than girls with a negative family history, while the opposite was true in boys; ie, family history-positive boys had a higher ratio than family history-negative boys. The association of a low ratio with a positive family history was seen most clearly in white girls. Family history-positive whites had higher ApoB than family history-negative whites, whereas the pattern was reversed in the blacks. The LDL-C/ApoB ratio and ApoB were not related to other CAD risk factors such as fatness, blood pressure, or other lipids and lipoproteins. Conclusion. In young children, a low LDL-C/ApoB ratio and high ApoB levels were associated with a positive family history of CAD only in the white girls, suggesting that this group is at increased risk of genetically mediated CAD.

scholarly journals The association between low-density lipoprotein cholesterol predicted by HMGCR genetic variants and breast cancer risk may be mediated by body mass index

2018 ◽  
Author(s):  
Siddhartha P. Kar ◽  
Hermann Brenner ◽  
Graham G. Giles ◽  
Dezheng Huo ◽  
Roger L. Milne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Nucleotide Polymorphisms ◽  
Low Density Lipoprotein Cholesterol ◽  
Genome Wide ◽  
A Genome ◽  
Mr Study

Orho-Melander et al. recently reported that lower low-density lipoprotein cholesterol (LDLC) as predicted by the T-allele of the variant rs12916 in HMGCR is associated with a decreased risk of developing breast cancer [odds ratio (OR) = 0.89; 95% confidence interval (CI): 0.82–0.96].1 This analysis was embedded in a wider Mendelian randomization (MR) study performed using genotype data from a prospective cohort of 26,589 individuals that included 16,022 women and 1176 incident breast cancer cases. HMGCR encodes 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the enzyme inhibited by statins. The T-allele of rs12916 is associated with reduced HMGCR expression and therefore, in principle, its effects should be analogous to the effects of lifelong statin administration starting at birth.2 The MR study of Orho-Melander et al. also found that a genome-wide LDLC score based on 32 independent LDLC-associated single nucleotide polymorphisms (SNPs) was not associated with breast cancer. In light of this finding, they suggest that the protective effect of the rs12916 T-allele on breast cancer may either be specific to LDLC lowering via genetic inhibition of HMGCR or be the result of a distinct mechanism that is regulated by rs12916 and HMGCR.

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