leky-latky/APOA2-gen/asociovane-choroby
Defects in this gene may result in
- Apolipoprotein A-II deficiency
- Hypercholesterolemia [1]
- protein homodimerization activity [4]
- Lipid binding [4]
- Homodimer; disulfide-linked [4]
- Forms a disulfide-linked heterodimer with APOD [4]
- Interacts with HCV core protein [4]
- Interacts with APOA1BP and NDRG1 [4]
Apolipoprotein A-II deficiency
- Deeb et al. (1990) identified homozygosity for a mutation in the APOA2 gene (107670.0001) [3]
APOLIPOPROTEIN A-II DEFICIENCY, FAMILIAL, DUE TO APOA-II (HIROSHIMA)
- APOA2, IVS3, G-A, +1
- Proband and her sister were homozygous for a G-to-A transition at position 1 of intron 3 of the APOA2 gene
- No immunologically detectable apolipoprotein A-II in her plasma
- Deficiency had little influence either on lipid and lipoprotein profiles or the occurrence of coronary artery disease [3]
Familial and Aapoaii Amyloidosis
Familial hypercholesterolemia
- APOA2 gene is linked to a gene that controls plasma levels of apoA-II
- APOA2 gene or its product influences, by an unknown mechanism, plasma levels of free fatty acids (FFA) [3]
- Lower levels of HDLC
- Higher apoA-II levels x unaffected
- Triglyceride and HDL-C levels were significant predictors of apoA-II levels
- ApoA-II variation is associated with several FCHL-related traits
- Heritability of apoA-II levels
- May have pleiotropic effects on apoA-II and FCHL traits
- ApoA-II is biochemically and genetically associated with FCHL
- May serve as a useful marker for understanding the mechanism by which FCHL develops [3]
- Through molecular study of a 1,135-member American Caucasian familial hypercholesterolemia (143890) kindred, Takada et al. (2002)
- SNP of the promoter of the APOA2 gene, -265T-C (107670.0002) influenced the level of
- Total cholesterol
- low density lipoprotein (LDL) cholesterol in members with a mutation in the LDLR gene causing hypercholesterolemia [3]
SNP of the promoter of the APOA2 gene, -265T-C
- Influenced the level of total cholesterol and low density lipoprotein (LDL) cholesterol in members with a mutation in the LDLR gene
- Causing hypercholesterolemia (606945.0063)
- Lower total cholesterol and LDL cholesterol values were observed among most of the LDLR mutation carriers
- Who were simultaneously homozygous for the -265C allele of the APOA2 gene [3]
- Transcriptional activity of the APOA2 promoter
- Reduced by 30% in the -265C allele as compared with the -265T allele [3]
Inzulínová rezistnece
- Studies in mice have revealed a role of APOA2 gene expression on insulin resistance, obesity and atherosclerosis
- With controversial results that have been attributed to dietary interactions [5]
APOA2, dietary fat, and body mass index: replication of a gene-diet interaction in 3 independent populations.
Cross-sectional, follow-up (20 years), and case-control analyses in 3 independent populations
- Gene-diet interactions
- APOA2 -265T>C polymorphism (rs5082) and saturated fat intake on BMI and obesity in 3462 individuals in the United States
- Framingham Offspring Study (1454 whites)
- Genetics of Lipid Lowering Drugs
- Diet Network Study (1078 whites)
- Boston-Puerto Rican Centers on Population Health and Health Disparities Study (930 Hispanics of Caribbean origin).
APOA2 -265T>C polymorphism (rs5082)
- No significant association of the APOA2 -265T>C SNP with HDL-C was found
- When SATFAT intake is low, the APOA2 -265T>C SNP does not affect BMI. However, when SATFAT intake is high, this SNP is strongly associated with BMI and obesity.
- In White-Americans, but also in US-Hispanics of Caribbean origin [5]
CC genotyp
- Prevalence 10.5% - 16.2%
- Difference in BMI between the individuals with the CC and TT+TC genotypes differed by saturated fat
- Mean increase in BMI of 6.2% (range, 4.3%-7.9%; P = .01)
- Between genotypes with high- (> or =22 g/d)
- 22g/d was established as the cut-off point to classify the low or the high SATFAT intake [5]
- But have demonstrated a linear dose-effect in the interaction [5]
- But not with low- saturated fat intake in all studies
- CC genotype was significantly associated
- with higher obesity prevalence in all populations only in the high-saturated fat stratum
- Meta-analysis estimations of obesity for individuals with the CC genotype
- CC subjects exhibited a higher association (B=0.108 Kg/m2; P=0.006) than carriers of the T-allele (B=0.033 Kg/m2; P=0.026) between SATFAT intake and BMI (P for interaction=0.021) [5]
- Impact of increased SATFAT intake on BMI increase was most noticeable for CC individuals, with the crossing point between the two regression lines at 22g/d of SATFAT, which was approximately the population mean. [5]
- Further adjustment of this interaction for physical activity did not alter the statistical significance of results [5]
