Apolipoprotein E polymorphisms and primary glaucoma in Saudis

Department of Ophthalmology, Armed Forces Hospital, Riyadh, Saudi Arabia.
Molecular vision (Impact Factor: 1.99). 02/2009; 15(94-96):912-9.
Source: PubMed


The frequencies of apolipoprotein E (APOE) alleles and genotypes were examined in 230 Saudi subjects including primary open-angle glaucoma (POAG; n=60) and primary angle-closure glaucoma (PACG; n=40) patients as well as 130 control subjects.
The presence of glaucoma in patients was based on clinical examination and/or ophthalmic records. The APOE allele frequency (epsilon2, epsilon3, and epsilon4) was studied by polymerase chain reaction (PCR) followed by reverse-hybridization and restriction fragment length polymorphism techniques.
Analysis of data showed a complete absence of epsilon2 allele and a significantly lower frequency of the epsilon3 allele in primary glaucoma patients (90.5%) compared to the control subjects (95.7%, p=0.034, relative risk [RR]=0.473, protective fraction [PF]=0.318). The frequency of the epsilon4 allele was significantly higher in the glaucoma patients (9.5%) compared to the control subjects (4.2%, p=0.034, RR=2.169, etiological fraction [EF]=0.329). The epsilon3/epsilon3 genotype was more common in controls than patients (p=0.060, RR=0.465, PF=0.322). The difference in genotype (epsilon3/epsilon4) was not statistically significant between the two groups (p=0.283). Genotype epsilon4/epsilon4 was found only in 3% of patients while being completely absent in the controls (p=0.080). The genotypes, epsilon2/epsilon2, epsilon2/epsilon3, and epsilon2/epsilon4, were absent in both the test and control groups. When patients were divided on the basis of types of glaucoma, POAG patients had a significantly higher frequency of epsilon4 allele and epsilon4/epsilon4 genotype than controls whereas there was no significant difference between PACG patient and control groups in frequencies of APOE alleles and genotypes.
This study indicates that the epsilon4 allele may be associated with POAG and could be a risk factor while epsilon3 may be protective for POAG, and APOE polymorphisms may not be associated at all with PACG in Saudis.

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    • "However, the studies did not provide any direct association with POAG but indicated a trend towards an association with IOP and age of onset of POAG. In addition, some studies have demonstrated moderate evidence for association of SNPs in TP53, NOS3, SEC14L2/TAP, and APOE [96,97,103,107]. However, these studies have been limited by sample size and would need further investigations in a large population-based cohort. "
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    ABSTRACT: Epidemiological studies suggest that by 2020 the prevalence of primary open angle glaucoma (POAG) is estimated to increase to 76.0 million, and to 111.8 million by 2040 globally due to the population aging. The prevalence of POAG is the highest among those of African descent, followed by Asians, and the lowest in Europeans. POAG is a genetically complex trait with a substantial fraction exhibiting a significant heritability. Less than 10% of POAG cases in the general population are caused by specific gene mutations and the remaining cases are polygenic. Quantitative traits related to POAG pathogenesis such as intra-ocular pressure (IOP), vertical cup/disc ratio (VCDR), optic disc area, and central corneal thickness (CCT) are highly heritable, and likely to be influenced at least in part by genes and show substantial variation in human populations. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) at different loci including CAV1/CAV2, TMCO1, CDKN2B-AS1, CDC7-TGFBR3, SIX1/SIX6, GAS7 and ATOH7 to be associated with POAG and its related quantitative traits (endophenotypes). The chapter provides a brief overview on the different GWAS and SNP association studies and their correlation with various clinical parameters important for POAG in the population worldwide, including the Middle East.
    Full-text · Article · Dec 2015 · International Journal of Molecular Sciences
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    • "However, compared with the Saudi Arabia Muslims who are believed to be the ancestors of the Chinese Hui ethnic people, the frequency of ε4 allele in the Hui ethnic group (3.9%) was close to that in the Arabs (3.9–6.3%) [27, 28]. "
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    ABSTRACT: The association, in different ethnic groups, of apolipoprotein E (apoE) gene polymorphism with mild cognitive impairment (MCI) has been unclear. Few studies have examined the association in Chinese minorities. The current study explores the association between apoE gene polymorphism and MCI in one of the biggest ethnic groups-the Hui-and compares it with the Han. The Minimental State Exam, Activities of Daily Living Scale, and Geriatric Depression Scale were administered to 306 ethnic Hui and 618 ethnic Han people aged ≥55 years. ApoE genotypes were determined using the high resolution melting curve method. The distribution of the apoE genotype and the frequency of alleles ε2, ε3, and ε4 were similar in the Hui and Han groups. In analyses adjusted for age, gender, and education level, the ε4 allele was a risk factor for MCI in both the Hui group (OR = 2.61, 95% CI: 1.02-6.66) and the Han group (OR = 2.36, 95% CI: 1.19-4.67), but the apoE ε2 allele was protective for MCI only in the Han group (OR = 0.48, 95% CI: 0.38-0.88). The association of some apoE genotypes with MCI may differ in different ethnic groups in China. Further studies are needed to explore this effect among different populations.
    Full-text · Article · Aug 2014 · International Journal of Alzheimer's Disease
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    • "Three studies on Asians and two studies on Caucasians examined the relationships between the APOE gene and high tension POAG (HTG), while three additional studies evaluated the association between the APOE gene and normal tension glaucoma (NTG). The HWE test was performed on the genotype distribution of the controls in all included studies, all of which showed p>0.05 in HWE, except four studies (two [26,31] showed p<0.05; two [34,37] lacked data). Detailed characteristics of each included study are presented in Table 1. "
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    ABSTRACT: Purpose To study the association of apolipoprotein E (APOE) polymorphisms and primary open-angle glaucoma (POAG). Methods After a systematic literature search, all relevant studies evaluating the association between APOE polymorphisms and POAG were included. All statistical tests were calculated with Stata 11.0. Results Twelve independent studies on the APOE gene (1,971 cases, 1,756 controls) and POAG were included. A significant association between the APOE gene and POAG was found in the genetic model of ε4/ε4 versus ε3/ε3 (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.12–3.88, p = 0.02). However, no association was detected in the models of ε2/ε2 versus ε3/ε3, ε2/ε3 versus ε3/ε3, ε2/ε4 versus ε3/ε3, ε3/ε4 versus ε3/ε3, allele ε2 versus allele ε3, and allele ε4 versus allele ε3. Subgroup analyses showed that a statistically significant association between the APOE gene and the risk of POAG existed in the genetic model of ε4/ε4 versus ε3/ε3 in Asians (OR = 3.55, 95% CI = 1.06–11.87, p = 0.04). No association was identified between the APOE gene and the risk of POAG in Caucasians. Conclusions The present meta-analysis indicated that the ε4/ε4 genotype is associated with increased risk of POAG in Asians.
    Full-text · Article · Jul 2014 · Molecular vision
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