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Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?

Corbo RM, Scacchi R

Ann. Hum. Genet., 1999 Jul;63(Pt 4):301-10.
PMID: 10738542

Apolipoprotein E (APOE = gene, apoE = protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In the present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populations with a long-established agricultural economy like those of the Mediterranean basin (0.849-0.898). The frequency of APOE*4, the ancestral allele, remains higher in populations like Pygmies (0.407) and Khoi San (0.370), aborigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Native Americans (0.280), and Lapps (0.310) where an economy of foraging still exists, or food supply is (or was until the recent past) scarce and sporadically available. The APOE*2 frequency fluctuates with no apparent trend (0.145-0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among human populations, could be identified as a 'thrifty' allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. The absence of the association of APOE*4 with CAD and AD in Sub-Saharan Africans, and its presence in African Americans, seems to confirm this hypothesis.

Matched MeSH terms: Coronary Disease/genetics
Coronary artery disease in Asians

Rajadurai J, Arokiasamy J, Pasamanickam K, Shatar A, Mei Lin O

Aust N Z J Med, 1992 Aug;22(4):345-8.
PMID: 1445022

From available studies, there appears to be a racial preponderance of coronary artery disease (CAD) among Indians when compared to other ethnic groups. We found that this racial difference exists even in a young Asian population with premature atherosclerosis. In this small series, these racial differences could not be explained by the commonly known risk factors for coronary artery disease--smoking, hypertension, diabetes and hypercholesterolaemia, findings similar to those found in older patients elsewhere. Only fasting triglyceride levels were significantly higher among young Indians compared to non Indians (p less than 0.02) although the importance of this finding as a risk factor for CAD remains controversial. The majority of these young patients were treated medically and their one year survival was good.

Matched MeSH terms: Coronary Disease/genetics
The association of mitochondrial DNA 5178 C > a polymorphism with plasma lipid levels among three ethnic groups

Lal S, Madhavan M, Heng CK

Ann. Hum. Genet., 2005 Nov;69(Pt 6):639-44.
PMID: 16266403

Mitochondria are eukaryotic cytoplasmic organelles responsible for oxidative phosphorylation. The C to A nucleotide transversion in the NADH dehydrogenase subunit 2 (MT-ND2) coding region of mitochondrial DNA has been reported to be associated with plasma lipid levels, adult onset diseases and longevity. We have examined the role of this polymorphism in relation to plasma lipid levels and age in a total of 713 healthy individuals belonging to 3 ethnic groups in Singapore. The frequency of the A allele was significantly higher (p < 0.05) among the Chinese (0.15) in comparison to the Malays (0.05) and Indians (0.02). No significant difference in the frequency of the allele was observed between healthy and coronary artery disease subjects, and between age-stratified subjects. We found that the polymorphism is significantly associated in an ethnic- and gender-specific manner with plasma apoB levels in the Chinese males (p < 0.05). This is the first epidemiological report of the mt5178 C > A polymorphism and its association with plasma lipid levels in Asian populations outside Japan.

Matched MeSH terms: Coronary Disease/genetics*
Variation of the platelet glycoprotein IIIa PI(A1/A2) allele frequencies in the three ethnic groups of Singapore

Lim J, Lal S, Ng KC, Ng KS, Saha N, Heng CK

Int J Cardiol, 2003 Aug;90(2-3):269-73.
PMID: 12957761

BACKGROUND: Polymorphisms of the glycoprotein IIIa receptor have been shown to be associated with differences in platelet aggregability. The PI(A2) variant of the polymorphism has been reported to be an inherited risk factor for acute coronary events. Although the allele frequency of this polymorphism is well documented in Caucasian populations, studies involving Asian Indians, Malays and Chinese are lacking. We studied 706 random male individuals to determine the genotypic distribution of this polymorphism in Singapore.
METHODS: Male subjects included in this study were drawn from those undergoing routine annual medical examinations offered by their employers. Venous blood was obtained from these patients after an overnight fast and from which genomic DNA was extracted. Genotyping was carried out by polymerase chain reaction (PCR) followed by digestion with restriction enzyme NciI. Personal and family medical history of the subjects were also taken.
RESULTS: The genotype distribution of the individuals studied was in accordance to a population at Hardy Weinberg equilibrium. The frequency of the PI(A2) allele was 0.1, 0.01 and 0.01 in the Indians, Malays and Chinese, respectively. The differences in frequencies of the PI(A2) variant are significant among different ethnic groups (P<0.001 for Indians vs. Chinese and Indians vs. Malays).
CONCLUSIONS: We observed a significantly higher frequency of the PI(A2) allele among Indians relative to the Chinese and Malays in Singapore. The effect of this genotype may partially explain the higher rate of ischaemic heart disease seen among Indians compared to the Chinese and Malay ethnic groups.

Matched MeSH terms: Coronary Disease/genetics
Serum HDL cholesterol and apolipoprotein AI, AII and B levels in Singapore newborns

Saha N, Wong HB

Biol. Neonate, 1987;52(2):93-6.
PMID: 3115319

The mortality from coronary artery disease (CAD) in Indians is more than three times that in the Chinese and Malays of Singapore. Serum total and HDL cholesterol as well as apolipoprotein (Apo) AI, AII and B levels were determined in a group of 349 newborns (cord blood) from both sexes in these three ethnic groups in order to examine if a trend is reflected at birth. Both serum LDL cholesterol and Apo B levels were low in the newborn, while HDL cholesterol and Apo AII levels were almost the same as in adults. Serum Apo AI levels were also low in newborns. No consistent difference as to ethnic group or sex was observed in any of the parameters investigated, except that the females had significantly higher levels of serum Apo AI in all the ethnic groups. Serum total and HDL cholesterol levels in Singapore newborns were comparable to those reported in Caucasians and Asians. The trends of incidence of CAD were not reflected in the lipid profiles studied at birth.

Matched MeSH terms: Coronary Disease/genetics
Fulltext Obesity in Malaysia

Ismail MN, Chee SS, Nawawi H, Yusoff K, Lim TO, James WP

Obes Rev, 2002 Aug;3(3):203-8.
PMID: 12164473 DOI: 10.1046/j.1467-789x.2002.00074.x

This study was undertaken to assess the recent data on Malaysian adult body weights and associations of ethnic differences in overweight and obesity with comorbid risk factors, and to examine measures of energy intake, energy expenditure, basal metabolic rate (BMR) and physical activity changes in urban and rural populations of normal weight. Three studies were included (1) a summary of a national health morbidity survey conducted in 1996 on nearly 29 000 adults > or =20 years of age; (2) a study comparing energy intake, BMR and physical activity levels (PALs) in 409 ethnically diverse, healthy adults drawn from a population of 1165 rural and urban subjects 18-60 years of age; and (3) an examination of the prevalence of obesity and comorbid risk factors that predict coronary heart disease and type 2 diabetes in 609 rural Malaysians aged 30-65 years. Overweight and obesity were calculated using body mass index (BMI) measures and World Health Organization (WHO) criteria. Energy intake was assessed using 3-d food records, BMR and PALs were assessed with Douglas bags and activity diaries, while hypertension, hyperlipidaemia and glucose intolerance were specified using standard criteria. The National Health Morbidity Survey data revealed that in adults, 20.7% were overweight and 5.8% obese (0.3% of whom had BMI values of >40.0 kg m(-2)); the prevalence of obesity was clearly greater in women than in men. In women, obesity rates were higher in Indian and Malay women than in Chinese women, while in men the Chinese recorded the highest obesity prevalences followed by the Malay and Indians. Studies on normal healthy subjects indicated that the energy intake of Indians was significantly lower than that of other ethnic groups. In women, Malays recorded a significantly higher energy intake than the other groups. Urban male subjects consumed significantly more energy than their rural counterparts, but this was not the case in women. In both men and women, fat intakes (%) were significantly higher in Chinese and urban subjects. Men were moderately active with the exception of the Dayaks. Chinese women were considerably less active than Chinese men. Chinese and Dayak women were less active than Malay and Indian women. In both men and women, Indians recorded the highest PALs. Hence, current nutrition and health surveys reveal that Malaysians are already affected by western health problems. The escalation of obesity, once thought to be an urban phenomenon, has now spread to the rural population at an alarming rate. As Malaysia proceeds rapidly towards a developed economy status, the health of its population will probably continue to deteriorate. Therefore, a national strategy needs to be developed to tackle both dietary and activity contributors to the excess weight gain of the Malaysian population.
Study name: National Health and Morbidity Survey (NHMS-2006)

Matched MeSH terms: Coronary Disease/genetics
ABCA1 gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore

Tan JH, Low PS, Tan YS, Tong MC, Saha N, Yang H, et al.

Hum Genet, 2003 Jul;113(2):106-17.
PMID: 12709788

Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.

Matched MeSH terms: Coronary Disease/genetics*
Fulltext The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD)

Akkaif MA, Daud NAA, Sha'aban A, Ng ML, Abdul Kader MAS, Noor DAM, et al.

Molecules, 2021 Apr 01;26(7).
PMID: 33915807 DOI: 10.3390/molecules26071987

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.

Matched MeSH terms: Coronary Disease/genetics*