ISID NEWS  •  December 2011 8

ISID Small Grant Program Report

Molecular Epidemiology of Hepatitis B Virus in Minangkabau Ethnic Group of West Sumatera, Indonesia

Marlinang D. Siburian,1 Mariana D.B. Intan,1 Ismail,1 Arnelis,2 Nasrul Zubir,2 Erlys B. Julianto,3 Andi Utama1

1MochtarRiadyInstituteforNanotechnology•Tangerang,Banten,Indonesia2M.DjamilHospital,Padang•WestSumatera,Indonesia3BloodTransfusionUnit,RedCrossPadang•WestSumatera,Indonesia

BackgroundHepatitisBvirus(HBV)infectionisassociatedwithadiverseclinicalspectrumofliverdamagerangingfromasymptomaticcarriers(AC),chronichepatitis(CH),livercirrhosis(LC),andhepatocellularcarcinoma(HCC).WHOestimatedabout2billionpeopleworldwidehavebeeninfectedbythevirusand350millionpeoplelivewithchronicHBVinfection.Indonesiawasreportedtohaveintermediatetohighendemicity[1].

Currentlythereareeightestablished(A–H)andtwoputative(I–J)HBVgenotypeswithdis-tinctgeographicaldistributions.GenotypeBandCarehighlyendemicinEastAsiaincludingIndonesia.TherearefourHBVgenotypesfoundinIndonesia(A–D),wheregenotypeBhasbeenfoundasthemajorgenotype[1–5].HBVgenotypeshavebeenreportedtoberelatedwithseverityofliverdisease.Forexample,genotypeChashigherdisease-inducingcapacitycomparedtogenotypeBinEastAsiancountriesthroughhighincidenceofcorepromotermutation[6–8].

MinangkabauisoneofthefourmajorethnicgroupsinIndonesiawithpopulationofapproxi-mately5.3million.TheyoriginallyresideintheWestSumateraprovince.PadangisthecapitalcityofWestSumaterawithapopulationofover833,000(census2010).ApreliminarystudyonHBVmolecularepidemiologyofMinangkabauethnicgroupprevaileddifferentprevalenceofHBVgenotypescomparetoIndonesianpopulationingeneral[4].Thisstudyaimedtofur-theranalyzetheprevalenceofHBVgenotypeinPadangpopulationandspecificallyMinangk-abauethnicgroup.

Materials and MethodsBloodsampleswerecollectedfromM.DjamilHospitalPadang,WestSumateraandBloodTransfusionUnit,RedCrossPadang,WestSumatera.Thesamplesweretakenfrom147blooddonors,and42liverdiseasepatientscomprisedof16CH,22LC,and4HCCpatients.Informedconsentwasobtainedfromeachparticipant.HBsAgtestforallsampleswereperformedbyacommerciallyavailableELISAkit(AbbottLaboratories,Chicago,IL).HBVDNAwasextractedfrom200μLplasmausingtheQIAampDNAbloodminikit(Qiagen,Hilden,Germany)accordingtothemanufacturer’sinstructions.HBVgenotype,subgenotypeandBCPdoublemutationweredeterminedaspreviouslydescribed[5,9].StatisticalanalyseswereperformedusingSPSS17.0softwareforWindows(SPSSInc.,Chicago,IL,USA)andP <0.05wasconsideredsignificant.

Results and DiscussionThestudyincludedatotalof189sampleswithpositiveHBsAgtest,165malesand24females.Themeanageofsubjectwas37.5±11.6yearsold.Of189samples,140(74.1%)and99(52.4%)sampleswerepositiveforgenotypingandsubgenotyping,respectively.GenotypeCwasfoundin84(60.0%)samples,genotypeBwasfoundin49(35.0%)samples,andmixgenotypesBandCwasfoundin7(5.0%)samples.Basedonitsethnicity,thesamplesweredividedintotwogroups:theMinangkabauethnicgroupandotherethnicsgroup,whichincludestheJavanese,Sundanese,Batak,andotherSumateraneseethnics.From189samples,98(70.0%)samplesbelongtoMinangkabauethnicgroup.Male/femaleratioandmeanageofthetwogroupsaresimilar.RatioofgenotypeBandCandmixgenotypeofB/CforMinangkabauethnicgroupandotherethnicsgroupwere19.4%:77.6%:3.1%and71.4%:19.1%:9.5%,respectively.Thegenotypedistributionbetweenthetwogroupsweresignifi-cantlydifferent(P<0.001).ThemajorsubgenotypesinthesamplesfromPadangwereC1(62.6%)

Marlinang D. Siburian

Ms. Siburian is a junior researcher

at the Mochtar Riady Institute

for Nanotechnology, Indonesia.

Her particular interest is in

Molecular epidemiology.

She has been working on

Molecular epidemiology of

Hepatitis B Virus and its

association with liver disease

in Indonesian population under

the supervision of Andi Utama

Ph.D and has co-authored in

some of the publications.

This research was supported with a grant from the International Society for Infectious Diseases (ISID).

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ISID NEWS  •  December 2011 9

ISID Small Grant Program Report continued

followedbyB3(24.2%)andB7(4.0%).IfwecomparedtheHBVgenotypeprevalencebetweenMinangkabauandotherethnicsgroups,itwasfoundthatintheMinangkabauethnicgroupthesubgenotypeC1(76.4%)wasmoredominantthansubgenotypeB3(18.1%),whileintheotherethnicgroupthemajorsubgenotypewasB3(40.7%)followedbysubgenotypesC1(25.9%)andB7(14.8%).

ThepresentstudyshowedthedifferenceofHBVgenotypeandsubgenotypedistributioninMinangkabauethniccomparedtothoseinIndonesianpopulationingeneral[4,5].HBVgenotypeCwithmajorityofsubgenotypeC1wasfoundasthemajorHBVgenotypeinPadang,specificallyinMinangkabauethnicgroup.AlthoughanotherstudyreportedthatHBVgenotypeCwasalsoprevalentintheeasternpartofIndonesia(MoluccasandPapua),themainsubgenotypesinthisareawereC5andC6[4,10],differentwithgenotypeCfoundinMinangkabauethnic.Inothercountries,HBVgenotypeCismoreprevalentinEastAsia,suchasinChinaandTaiwan.LongitudinalcohortstudiesinTaiwandemonstratedthatHBVgenotypeCisanindependentriskfactorforHCCdevelopmentandisassociatedwithahigherriskofreactivationofhepatitisBandprogressiontocirrhosisthanHBVgenotypeB[11-13].Longitudinalcohortstudyneedstobeperformedinordertoinvestigatetheassocia-tionofHBVgenotypeCandriskofHCCinMinangkabaupopulation.

ConclusionsTheHBVgenotypedistributioninthepopulationofMinangkabauethnicisdifferentthanthatofotherIndonesianHBVcarrieringeneral.MinangkabauethnicgrouphashigherprevalenceofHBVgenotypeCthanotherethnicsgroup(77.6%vs19.1%).SubgenotypeC1andB3arethemajorsubgenotypesfoundinthisethnicgroup.ThesepreliminaryresultsindicatethattheMinangkabauethnicgroupmaybeathigherriskofdevelopingsevereliverdisease.

This study was supported by a grant from the International Society for Infectious Diseases (ISID) under the Small Grants Program. We thank Rama Dhenni for the assistance in blood sample collections.

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ISID Small Grant Report of

Marlinang D. SiburianMolecular Epidemiology of Hepatitis B Virus in

Minangkabau Ethnic Group of West Sumatera, Indonesia

This research was supported with a grant from the International Society for Infectious Diseases (ISID).