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POSTERS:MolecularBiology
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OF TvaosmE BVDROXVLA5E ASSENCEOF LINKAGE AND ASSOCUTION m SSVPERTENSION.P Shsrma, MICSC+VATSLLtTEMARKSR TO ESSENTIAL A
A Hingorani,H lie, RHopPr, M J BrownClinicsJPhamrscology u CambridgeUniversity,Addenbrooke’s Hospitsf,CambridgeUK a The geneticcontributionof assendsf b~rtension (3TT)has yet to be elucidated.Tyroainehydroxyleae(TJ-J)is the rate limiting enzyme in ~ cerecholsminebiosynthesis end is a candidstegenefor the aetiologvof o e e HT. TM gene contains en intertsst informative(heterozygosityQ.75) r microsatellitemarker (TCA’f)9which w used to undertake, (i) an associationstudyin a groupof well characterizedhypertensive @Tl) m snd mntml ~ subjects,and; (ii) an affectedsibling@r (ASP)study y using sibships from our Iocaf family practices 227 hypertensive patients (pretreatment BP range 139/94 - 237/133 nrmHg: age rangeJSD;30-71/5.5)were age anda sex matched with 206 control z subjects(with BP range 96/62 - 153/S6nunHg: age rsnge/SD; 40t 70/7.6).136sffectedsiblingpairs wererecruitedfor our linkagestudy. AHsubjectswere Caucasian.TH markerwas smplisiedusing standard PCRcyclingconditionsin efl subjectsendpmrfuctsweremn on an ABI x 373A sequencer.TH efleles were assigned using Oenesan@ and
[email protected] TH aJleleswere present end designsted A-E. AfIelefrequenciesin NT population(A, B, C, D, E: 0.24, 0.17, 0.13, 0.20, 0.26, respectively)were similar to those in HTl (A, B, C, D, E: frequencieswere 0.24, 0.19, 0.11, 0.11, 0.35, respwtively).G
[email protected]). Bothgroupswerein Hardy-Weinbergpropmtion. Muftiple regressionansfysis showed that TH genotypewas not en i y i independentpredictorof either SBP or DBP in NT m HTl cohorts. Othercovariatessuchas age, sex, sfmhol, cigaretteamofdng,BMJand cholesterolSJSOshowed no signincant relationship with BP. ASP linkage&ta was ansfysedusing SPLINK,a non-parametricprogram. o Expectedvakuesfor 20, 21 end 22 (sflele sharing of 25%, 50% and x 25%, respectively)wers calculatedas 34,a 6S and 34, respectivelyand comparedwith obsetvedwdues of 36.S, 67.9 and 31.3, respectively. r a ay There was no excess sharing of TH sfteles amongst atTectEYJ sibling ? f e pairs (FO.59; LOD scor&O.0).We have failed x
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