Human APOE gene is located in 19ql3.2 region of the human genome. The gene codes for a protein called apolipoprotein E. The protein involved in lipid metabolism, regulation of blood cholesterol level and some other important cell functions. Allele’s e2, e3, and e4 are the most spread in humans. Level of cholesterol is the highest in e4 allele carriers, medium for e3 and the lowest for e2 carriers. The high cholesterol level associated with e4 allele is a risk factor for cardiovascular diseases and Alzheimer disease in westernized societies but not in African hunter-gatherers. We have established APOE allele frequencies in Iranians and Pamir population as well as in some populations of Russia (Russians, Ukrainians and Byelorussians). E3 allele and e3/e3 genotype were found the most spread in all of the populations with frequencies 0.74-0.80 and 0.60-0.64 correspondingly. We also screened for available information on APOE allele frequencies and found the data for 144 populations from different parts of the world. We have found that АРОЕ *е4 allele frequencies have a latitudinal distribution in all parts of the world. Minimum e4 frequency (3-5%) as well as maximum e3 frequency (>90%) was found in populations inhabiting areas at the latitude that corresponds to the Northern tropic. The e4 allele frequencies are growing rather symmetrically both to the north and to the south from the latitude. Spearman`s correlation coefficient between the e4 allele frequency and the latitude is high and valid both for populations to the north from the tropic (rho=0.67, P< 0.001) and for populations to the south from the tropic (rho =0.46, p0.001). For each 200 of latitude the frequency is going 10% up for the northern populations and 20% up for the southern populations. The latitudinal distribution of e3 allele frequencies is a mirror distribution for e4 frequency. Spearman`s correlation coefficient is both high and valid for the northern populations (rho=0.66, P< 0.001) and for the southern populations (rho= 0.45, P< 0.00I). The latitudinal distribution is absent for e2 allele frequencies. The e4 frequencies are closer to each other for populations inhabiting the same latitude. The same is true for e3 allele frequencies. The phenomenon can be seen even for populations of the same latitude inhabiting different continents. That means that the distribution does not reflect a trace of human migrations. We believe that both APOE* e4 and e3 alleles, but not el allele, may be associated with adaptation of humans to climate conditions.      

Objective(s): The human apolipoprotein E4 (APOE4) is associated with various brain injuries and neurodegenerative changes. Curcumin is an active ingredient isolated from the root of turmeric and is believed to have therapeutic effects on neurodegenerative diseases. The aim of this study was to investigate the effects of curcumin on APOE4-induced neurological damage and explore its molecular mechanisms. Materials and Methods: SH-SY5Y cells were pretreated with curcumin for 24 hr and transfected with human APOE4 gene using Lipofectamine 2000. Then, the effect of curcumin on the transfected cells was detected by ELISA, immunofluorescence staining and Western blot. Results: The production or expression of proinflammatory cytokines and proteins, including tumor necrosis factor-α (TNF-α ), interleukin-1β (IL-1β ), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was significantly increased in SH-SY5Y cells transfected with APOE4, and curcumin inhibited APOE4-induced cellular inflammatory damage. Western blot analysis showed that, after transfection with APOE4, the expression of total nuclear factor kappa B (NF-κ B) p65 and p-NF-κ B p65 in the nucleus was increased, and curcumin inhibited the nuclear translocation of p65. The overexpression of APOE4 inhibited the expression of peroxisome proliferator-activated receptor-γ (PPARγ ), whereas curcumin reversed and increased the expression of PPARγ protein. Down-regulating PPAR-γ with the inhibitor GW9662 and the shPPARγ gene confirmed that the NF-κ B signaling pathway was inhibited by PPARγ . Conclusion: This study suggests that APOE4 overexpression can induce cellular inflammatory damage, and pretreatment of curcumin could exert an anti-inflammatory effect by upregulating the expression of PPARγ to inhibit the activation of NF-κ B signaling pathway.

Background: The role of apolipoprotien E polymorphisms do not diagnostic correctly in recurrent pregnancy loss etiology but Apo E has been shown to play an important role in lipid metabolism in pregnancy. We evaluated these polymorphisms in Iranian women with unexplained recurrent pregnancy loss.Materials and Methods: 5 ml Blood were sampling from 81 women with a history of two or more consecutive spontaneous abortions and 81 women with at least two live births and not miscarriage. DNA was extracted from the leukocytes and PCR amplification of Apo E was performed.For determining Apo E genotypes used restriction fragment length polymorphism analysis.Results: Women with consecutive spontaneous abortions had greater significantly frequency from Apo E E3/ E4 and E4/E4 genotype (19.75%) comparing with control group (2.46%) (p=0.032).Conclusion: Polymorphism Apo E4 may help to thrombophilic risk factors in loss of fetus during pungency. Our data supported association polymorphisms apolipoprotein E with recurrent pregnancy loss.

Background: Thrombophilia has been viewed as a multigenic disorder rather than a monogenetic clinical phenotype and Apo E has been shown to play an important role in lipid metabolism in pregnancy. As individuals carrying the E4 allele of the Apo E gene have the highest risk for thrombosis, we evaluated the frequency of the Apo E4 genotype among women suffering from recurrent pregnancy loss.Materials and Methods: 81 women with a history of two or more consecutive spontaneous abortions were examined for their APO-E genotypes based on restriction fragment length polymorphism analysis of PCR amplified fragments including amino acid positions 112 and 158.The observed genotypes were compared with negative controls.Results: Women experiencing recurrent pregnancy loss had a significantly higher prevalence of Apo E3/4, E4/4 genotypes (19.75%) compared with control women (2.46%) (p=0.00001).Conclusion: Apo E4 polymorphism may contribute to the thrombophilic risk factors contributing to recurrent pregnancy loss.