Analysis of apolipoprotein E genetic polymorphism in a large ethnic Hakka population in southern China

Zhong, Zhixiong; Wu, Heming; Wu, Hesen; Zhao, Pingsen

doi:10.1590/1678-4685-GMB-2017-0301

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Human and Medical Genetics • Genet. Mol. Biol. 41 (4) • Oct-Dec 2018 • https://doi.org/10.1590/1678-4685-GMB-2017-0301 copy

Analysis of apolipoprotein E genetic polymorphism in a large ethnic Hakka population in southern China

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

There is currently no data about the genetic variations of APOE in Hakka population in China. The aim of this study was to analyze the allelic and genotypic frequencies of APOE gene polymorphisms in a large ethnic Hakka population in southern China. The APOE genes of 6,907 subjects were genotyped by the gene chip platform. The allele and genotype frequencies were analyzed. Results showed that the ∊3 allele had the greatest frequency (0.804) followed by ∊2 (0.102), and ∊4 (0.094), while genotype ∊3/∊3 accounted for 65.43% followed by ∊2/∊3 (15.85%), ∊3/∊4 (14.13%), ∊2/∊4 (3.01%), ∊4/∊4 (0.84%), and ∊2/∊2 (0.74%) in all subjects. The frequencies of the ∊4 allele in Chinese populations were lower than Mongolian and Javanese, while the frequencies of the ∊2 allele were higher and ∊4 allele lower than Japanese, Koreans, and Iranian compared with the geographically neighboring countries. The frequencies of ∊2 and ∊4 alleles in Hakka population were similar to the Vietnamese, Chinese-Shanghai, Chinese-Kunming Han and Chinese-Northeast, and French. The frequency of ∊2 in Hakka population was higher than Chinese-Dehong Dai and Chinese-Jinangsu Han. The low frequency of the APOE ∊4 allele may suggest a low genetic risk of Hakka population for cardiovascular disease, Alzheimer’s disease, and other diseases.

Keywords:
Apolipoprotein E; genetic polymorphism; Hakka; southern China; genotyping

APOE	Male (n=4366)			Female (n=2541)			Combined (n=6907)
	n	Frequency	%	n	Frequency	%	n	Frequency	%
Allele
∊2	899	0.103		506	0.100		1405	0.102
∊3	7016	0.803		4093	0.805		11109	0.804
∊4	817	0.094		483	0.095		1300	0.094
Genotype
∊2/∊2	29		0.66	22		0.87	51		0.74
∊2/∊3	710		16.26	385		15.15	1095		15.85
∊2/∊4	131		3.00	77		3.03	208		3.01
∊3/∊3	2851		65.30	1668		65.64	4519		65.43
∊3/∊4	604		13.83	372		14.64	976		14.13
∊4/∊4	41		0.94	17		0.67	58		0.84

Populations	Total Number	Alleles frequency of APOE			References
		∊2	∊3	∊4
Asians
Chinese
Chinese-Hakka	6907	0.102	0.804	0.094	This work
Chinese-Shanghai	266	0.098	0.786	0.116	*Yang et al.,* 2003**Yang JD, Feng GY, Zhang J, Cheung J, St Clair D, He L and Ichimura K (2003) Apolipoprotein E-491 promoter polymorphism is an independent risk factor for Alzheimer’s disease in the Chinese population. Neurosci Lett 350:25-28.
Chinese-Dehong Dai	171	0.064	0.889	0.047	*Tang et al.,* 2005**Tang H, Yan X, Hua Y, Wei M, Zhang L, Gao J and Dong H (2005) Distribution of apoE polymorphism in Chinese Yunnan Dehong Dai ethnic group. Chin J Med Genet 22:224-226.
Chinese- Jinangsu Han	168	0.071	0.863	0.066	*Liang et al.,* 2009**Liang S, Pan M, Geng HH, Chen H, Gu LQ, Qin XT, Qian JJ, Zhu JH and Liu CF (2009) Apolipoprotein E polymorphism in normal Han Chinese population: frequency and effect on lipid parameters. Mol Biol Rep 36:1251-1256.
Chinese-Kunming Han	71	0.092	0.852	0.056	*Tang et al.,* 2005**Tang H, Yan X, Hua Y, Wei M, Zhang L, Gao J and Dong H (2005) Distribution of apoE polymorphism in Chinese Yunnan Dehong Dai ethnic group. Chin J Med Genet 22:224-226.
Chinese-Northeast	69	0.096	0.824	0.081	*Zhou et al.,* 2005**Zhou J, Xue YL, Guan YX, Yang YD, Fu SB and Zhang JC (2005) Association study of apolipoprotein e gene polymorphism and cerebral infarction in type 2 diabetic patients. Hereditas 27:35-38.
Indian	4450	0.039	0.887	0.073	*Thelma et al., 2001*Thelma BK, Juyal RC, Dodge HH, Pandav R, Chandra V and Ganguli M (2001) APOE polymorphism in a rural older population-based sample in India. Hum Biol 73:135-144.
Japanese	1097	0.048	0.851	0.101	*Hallmann et al.,* 1991Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csázár A and Utermann G (1991) The apolipoprotein E polymorphism: A comparison of allele frequencies and effects in nine populations. Am J Hum Genet 49:338-349.; Gerdes et al., 1992**Gerdes LU, Klausen IC, Sihm I, Faergeman O and Vogler GP (1992) Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genet Epidemiol 9:155-167.
Mongolian	744	0.037	0.808	0.155	*Svobodová et al.,* 2007a**Svobodová H, Kucera F, Stulc T, Vrablík M, Amartuvshin B, Altannavch T and Ceska R (2007a) Apolipoprotein E gene polymorphism in the Mongolian population. Folia Biol 53:138-142.
Vietnamese	348	0.090	0.790	0.120	*Nghiem et al.,* 2004**Nghiem NT, Ta TT, Ohmori R, Kuroki M, Nguyen VC, Nguyen TK, Kawakami M and Kondo K (2004) Apolipoprotein E polymorphism in Vietnamese children and its relationship to plasma lipid and lipoprotein levels. Metabolism 53:1517-1521.
Malay	223	0.140	0.620	0.240	*Gajra et al.,* 1994a**Gajra B, Candlish JK, Saha N, Heng CK, Soemantri AG and Tay JSH (1994b) Influence of polymorphisms for Apolipoprotein-B (Ins/Del XbaI, EcoR1) and Apolipoprotein-E on serum lipids and apolipoproteins in a Javanese population. Genet Epidemiol 11:19-27
Javanese	197	0.060	0.770	0.170	*Gajra et al.,* 1994b**Gajra B, Candlish JK, Saha N, Mak JW and Tay JSH (1994a) Effect of Apolipoprotein-E variants on plasma lipids and apolipoproteins in the Orang-Asli (Aborigines) of Malaysia. Hum Hered 44:209-213
Koreans	145	0.020	0.870	0.110	*Hong et al.,* 1997**Hong SH, Kang BY, Oh JH, Kim JQ and Lee CC (1997) Genetic variations of the Apo E-CI-CII cluster gene in Koreans. Clin Biochem 30:215-219.
Iranian	129	0.027	0.912	0.061	*Raygani et al., 2005*Raygani AV, Zahrai M, Raygani AV, Doosti M, Javadi E, Rezaei M and Pourmotabbed T (2005) Association between apolipoprotein E polymorphism and Alzheimer disease in Tehran, Iran. Neurosci Lett 375:1-6.
Europeans
Dutch	2318	0.085	0.752	0.163	*Smit et al., 1988Smit M, de Knjiff P, Rosseneu M, Bury J, Klasen E, Frants R and Havekes L (1988) Apolipoprotein E polymorphism in The Netherlands and its effect on plasma lipid and apolipoprotein levels. Hum Genet 80:287-292.; Knjiff et al., 1993*Knjiff P, Boomsma DI, Wit E, Kempen HJM, Leuven JAG, Frants RR and Havekes LM (1993) The effect of the apolipoprotein E phenotype on plasma lipids is not influenced by environmental variability: Results of a Dutch twin study. Hum Genet 91:268-272.
Finnish	2245	0.044	0.748	0.208	*Lehtimäki et al., 1990Lehtimäki T, Moilanen T, Viikari J, Akerblom HK, Ehnholm C, Rönnemaa T, Marniemi J, Dahlen G and Nikkari T (1990) Apolipoprotein E phenotypes in Finnish youths: A cross-sectional and 6-year follow-up study. J Lipid Res 31:487-495.; Salo et al., 1993Salo MK, Rantanen R, Huupponen T, Lehtimäki T and Jokela H (1993) Apolipoprotein E phenotypes and plasma lipids in diabetic children and adolescents. Eur J Pediatr 152:564-568.; Hallman et al.,* 1991**Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csázár A and Utermann G (1991) The apolipoprotein E polymorphism: A comparison of allele frequencies and effects in nine populations. Am J Hum Genet 49:338-349.
Germans	1211	0.083	0.784	0.133	*Kolovou et al.,* 2009**Kolovou GD, Anagnostopoulou KK and Cokkinos DV (2009) Apolipoprotein E gene polymorphism and myocardial infarction. Int J Cardiol 133:264-265.
Italians	2000	0.060	0.849	0.091	*Corbo et al.,* 1995**Corbo RM, Scacchi R, Mureddu L, Mulas G and Alfano G (1995) Apolipoprotein-E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique – comparison with frequency data of other European populations. Ann Hum Genet 59:197-209.
Spanish	1286	0.052	0.856	0.091	*Valveny et al., 2010Valveny N, Esteban E, Kandil M and Moral P (2010) APO E polymorphism in Spanish and Moroccan populations. Clin Genet 51:354-356.; Gerdes et al.,* 1992Gerdes LU, Klausen IC, Sihm I, Faergeman O and Vogler GP (1992) Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genet Epidemiol 9:155-167.; Lucotte et al., 1997*Lucotte G, Loirat F and Hazout S (1997) Pattern of gradient of apolipoprotein E allele 4 frequencies in western Europe. Hum Biol 69:253-262.; Muros and Rodríguez-Ferrer, 1996Muros M and Rodríguez-Ferrer C (1996) Apolipoprotein E polymorphism influence on lipids, apolipoproteins and Lp(a) in a Spanish population underexpressing apo E4. Atherosclerosis 121:13-21.
French	1228	0.108	0.771	0.121	*Bailleul et al.,* 1993Bailleul S, Couderc R, Landais V, Lefèvre G, Raichvarg D and Etienne J (1993) Direct phenotyping of human apolipoprotein E in plasma: application to population frequency distribution in Paris (France). Hum Hered 43:59-165.; Gueguen et al., 1989Gueguen R, Visvikis S, Steinmetz J, Siest G and Boerwinkle E (1989) An analysis of genotype effects and their interactions by using the apolipoprotein E polymorphism and longitudinal data. Am J Hum Genet 45:793-802.; Boerwinkle et al., 1986**Boerwinkle E, Chakraborty R and Sing CF (1986) The use of measured genotype information in the analysis of quantitative phenotypes in man. Ann Hum Genet 50:181-194.
Belgians	189	0.069	0.762	0.169	*Engelborghs et al., 2003*Engelborghs S, Dermaut B, Goeman J, Saerens J, Mariën P, Pickut BA, Van den Broek M, Serneels S, Cruts M, Van Broeckhoeven C and De Deyn PP (2003) Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects. J Neuro Neurosur Ps 74:1148-1151.
UK	734	0.089	0.767	0.144	*Corbo et al.,* 1995Corbo RM, Scacchi R, Mureddu L, Mulas G and Alfano G (1995) Apolipoprotein-E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique – comparison with frequency data of other European populations. Ann Hum Genet 59:197-209.; Lucotte et al., 1997*Lucotte G, Loirat F and Hazout S (1997) Pattern of gradient of apolipoprotein E allele 4 frequencies in western Europe. Hum Biol 69:253-262.
Greeks	551	0.054	0.878	0.068	*Marios et al., 1995Marios ACPD, Kokkofitou A, Manoli P, Christou S, Karagrigoriou A and Middleton L (1995) Underexpression of the apolipoprotein E2 and E4 alleles in the Greek Cypriot population of Cyprus. Genet Epidemiol 12:489-497.; Sklavounou et al., 2010*Sklavounou E, Economou-Petersen E, Karadima G, Panas M, Avramopoulos D, Varsou A, Vassilopoulos D and Petersen MB (2010) Apolipoprotein E polymorphism in the Greek population. Clin Genet 52:216-218.
Danish	466	0.085	0.741	0.174	*Gerdes et al.,* 1992**Gerdes LU, Klausen IC, Sihm I, Faergeman O and Vogler GP (1992) Apolipoprotein E polymorphism in a Danish population compared to findings in 45 other study populations around the world. Genet Epidemiol 9:155-167.
Swedish	407	0.077	0.740	0.190	*Roussos et al., 2004*Roussos L, Ekström U, Ehle PN, Oqvist B and Floren CH (2004) Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in Sweden. Scand J Urol Nephrol 38:504-510.
Turks	90	0.063	0.868	0.069	*Brega et al., 1998*Brega A, Scacchi R, Cuccia M, Kirdar B, Peloso G and Corbo RM (1998) Study of 15 protein polymorphisms in a sample of the Turkish population. Hum Biol 70:715-728.
Africans
Nigeria	1562	0.064	0.684	0.252	*Kamboh et al., 2015*Kamboh MI, Bunker CH, Aston CE, Nestlerode CS, McAllister AE and Ukoli FA (2015) Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African blacks. Genet Epidemiol 16:205-222.
Algerian	732	0.050	0.846	0.104	*Boulenouar et al., 2013*Boulenouar H, Benchekor SM, Meroufel DN, Hetraf SAL, Djellouli HO, Hermant X, Grenierboley B, Medjaoui IH, Mehtar NS and Amouyel P (2013) Impact of APOE gene polymorphisms on the lipid profile in an Algerian population. Lipids Health Dis 12:155.
Sub-Saharans	470	0.116	0.706	0.178	*Zekraoui et al., 1997Zekraoui L, Lagarde JP, Raisonnier A, Gérard N, Aouizérate A and Lucotte G (1997) High frequency of the Apolipoprotein E 4 allele in African Pygmies and most of the African populations in sub-Saharan Africa. Hum Biol 69:575-581.
Nigerians	365	0.027	0.677	0.296	*Sepehrnia et al., 1989*Sepehrnia B, Kamboh MI, Adams-Campbell LL, Bunker CH, Nwankwo M, Majumder PP and Ferrell RE (1989) Genetic studies of human apolipoproteins. X. The effect of the apolipoprotein E polymorphism on quantitative levels of lipoproteins in Nigerian blacks. Am J Hum Genet 45:586-591.
Khoi San	247	0.077	0.553	0.370	*Sandholzer et al., 1995*Sandholzer C, Delport R, Vermaak H and Utermann G (1995) High frequency of the apo epsilon 4 allele in Khoi San from South Africa. Hum Genet 95:46-48.
North Americans
American- whites	702	0.082	0.778	0.140	*Djoussé et al., 2004*Djoussé L, Pankow JS, Arnett DK, Eckfeldt JH, Myers RH and Ellison RC (2004) Apolipoprotein E polymorphism modifies the alcohol-HDL association observed in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr 80:1639-1644.
South Americans
Brazil	2010	0.063	0.797	0.140	*Fuzikawa et al., 2007Fuzikawa AK, Peixoto SV, Taufer M, Moriguchi EH and Lima-Costa MF (2007) Apolipoprotein E polymorphism distribution in an elderly Brazilian population: the Bambui Health and Aging Study. Braz J Med Biol Res 40:1429-1434.; França et al.,* 2004França ED, Alves JGB and Hutz MH (2004) Apolipoprotein E Polymorphism and Its Association with Serum Lipid Levels in Brazilian Children. Hum Biol 76:267-275.; Brito et al., 2011Brito DD, Fernandes AP, Gomes KB, Coelho FF, Cruz NG, Sabino AP, Cardoso JE, Figueiredo-Filho PP, Diamante R and Norton CR (2011) Apolipoprotein A5-1131T > C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents. Mol Biol Rep 38:4381-4388.; Souza et al., 2003**Souza DR, Godoy MR, Hotta J, Tajara EH, Brandão AC, Pinheiro JS, Tognola WA and Santos JE (2003) Association of apolipoprotein E polymorphism in late-onset Alzheimer’s disease and vascular dementia in Brazilians. Braz J Med Biol Res 36:919-923.
Venezuela	1841	0.055	0.834	0.111	*Molero et al.,* 2001Molero A, Pino-Ramirez G and Maestre G (2001) Modulation by age and gender of risk for Alzheimer’s disease and vascular dementia associated with the apolipoprotein E-varepsilon4 allele in Latin Americans: Findings from the Maracaibo Aging Study. Neurosci Lett 307:5-8.; Arráiz et al., 2010**Arráiz N, Bermúdez V, Prieto C, Sánchez MP, Escalona C, Sanz E, Rondón N, Reyes F and Velasco M (2010) Association between apoliprotein E gene polymorphism and hypercholesterolemic phenotype in Maracaibo, Zulia state, Venezuela. Am J Ther 17:330-336.
Colombia	1001	0.075	0.814	0.111	*Velez-Pardo et al., 2015*Velez-Pardo C, Rojas W, Jimenez-Del-Rio M and Bedoya G (2015) Distribution of APOE polymorphism in the “Paisa” population from northwest Colombia (Antioquia). Ann Hum Biol 42:195-198.

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[1] Send correspondence to Pingsen Zhao. Clinical Core Laboratory, Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou 514031, P.R. China. E-mail: zhaopingsen01@163.com, zhaopingsen@hotmail.com.