中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2009年
4期
223-228
,共6页
聂玲%艾晓非%郑以州%李庆华%杨琳%肖志坚
聶玲%艾曉非%鄭以州%李慶華%楊琳%肖誌堅
섭령%애효비%정이주%리경화%양림%초지견
基因%HFE%突变%骨髓增生异常综合征%贫血%再生障碍%铁代谢障碍
基因%HFE%突變%骨髓增生異常綜閤徵%貧血%再生障礙%鐵代謝障礙
기인%HFE%돌변%골수증생이상종합정%빈혈%재생장애%철대사장애
Gene,HFE%Mutations%Myelodysplastic syndromes%Aplastic anemia%Iron metabolism
目的 分析健康正常人、骨髓增生异常综合征(MDS)和再生障碍件贫血(AA)患者HFE基因突变的频率并探讨其与铁代谢和铁过载脏器功能受损相关指标的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)联合测序分析的方法检测271例MDS患者、402例从患者和1615名健康正常对照的HFE基因H63D和C282Y突变,并比较未输注红细胞的MDS和AA患者HFE基因突变组与未突变组的铁代谢指标和铁过载脏器功能受损相关指标.结果 271例MDS患者、402例AA患者及1615名正常对照中均未发现HFE基因C282Y突变及C282Y和H63D复合突变.MDS患者H63D突变率为4.1%(271例中11例),且均为杂合型.从患者H63D杂合型突变率为9.7%(402例中39例),纯合型突变率0.25%(402例中1例).正常对照H63D杂合型突变率为10.2%(164例),纯合型突变率0.24%(4例).MDS患者H63D突变率明显低于正常对照(P:0.002),而AA患者与正常对照比较差异无统计学意义(P=0.988).未输注红细胞的MDS及AA患者的血清铁蛋白(SF)值、血清铁(SI)值、铁饱和度(TS)值均接近或高于正常高限,血清未饱和铁(UIBC)值明显低于正常.未输注红细胞的MDS患者H63D突变组与未突变组的SF、SI、UIBC、总铁结合力(TIBC)、TS值差异无统计学意义(P值均＞0.05);未输注红细胞的AA患者H63D突变绀的SI值明显高于未突变组[42.6(24.6～60.4)μmol/L和32.0(8.4～63.3)μmol/L(P=0.011)],而两组的其他铁代谢参数差异均无统计学意义(P值均＞0.05).MDS及AA患者或就诊前未输注红细胞的MDS及AA患者H63D突变组与未突变组的肝酶值、卒腹血糖(FBS)值、心电图(ECG)异常率、外周血指标差异均无统计学意义(P值均＞0.05).结论 HFE基因H63D和C282Y突变在人群的分布有种族和遗传的差异,中国人HFE基因的突变率明显低于白种人.MDS与AA患者本身均可致铁过载,HFE基因H63D和C282Y突变并不是导致其铁过载的主要原因.
目的 分析健康正常人、骨髓增生異常綜閤徵(MDS)和再生障礙件貧血(AA)患者HFE基因突變的頻率併探討其與鐵代謝和鐵過載髒器功能受損相關指標的關繫.方法 採用聚閤酶鏈反應-限製性片段長度多態性(PCR-RFLP)聯閤測序分析的方法檢測271例MDS患者、402例從患者和1615名健康正常對照的HFE基因H63D和C282Y突變,併比較未輸註紅細胞的MDS和AA患者HFE基因突變組與未突變組的鐵代謝指標和鐵過載髒器功能受損相關指標.結果 271例MDS患者、402例AA患者及1615名正常對照中均未髮現HFE基因C282Y突變及C282Y和H63D複閤突變.MDS患者H63D突變率為4.1%(271例中11例),且均為雜閤型.從患者H63D雜閤型突變率為9.7%(402例中39例),純閤型突變率0.25%(402例中1例).正常對照H63D雜閤型突變率為10.2%(164例),純閤型突變率0.24%(4例).MDS患者H63D突變率明顯低于正常對照(P:0.002),而AA患者與正常對照比較差異無統計學意義(P=0.988).未輸註紅細胞的MDS及AA患者的血清鐵蛋白(SF)值、血清鐵(SI)值、鐵飽和度(TS)值均接近或高于正常高限,血清未飽和鐵(UIBC)值明顯低于正常.未輸註紅細胞的MDS患者H63D突變組與未突變組的SF、SI、UIBC、總鐵結閤力(TIBC)、TS值差異無統計學意義(P值均＞0.05);未輸註紅細胞的AA患者H63D突變紺的SI值明顯高于未突變組[42.6(24.6～60.4)μmol/L和32.0(8.4～63.3)μmol/L(P=0.011)],而兩組的其他鐵代謝參數差異均無統計學意義(P值均＞0.05).MDS及AA患者或就診前未輸註紅細胞的MDS及AA患者H63D突變組與未突變組的肝酶值、卒腹血糖(FBS)值、心電圖(ECG)異常率、外週血指標差異均無統計學意義(P值均＞0.05).結論 HFE基因H63D和C282Y突變在人群的分佈有種族和遺傳的差異,中國人HFE基因的突變率明顯低于白種人.MDS與AA患者本身均可緻鐵過載,HFE基因H63D和C282Y突變併不是導緻其鐵過載的主要原因.
목적 분석건강정상인、골수증생이상종합정(MDS)화재생장애건빈혈(AA)환자HFE기인돌변적빈솔병탐토기여철대사화철과재장기공능수손상관지표적관계.방법 채용취합매련반응-한제성편단장도다태성(PCR-RFLP)연합측서분석적방법검측271례MDS환자、402례종환자화1615명건강정상대조적HFE기인H63D화C282Y돌변,병비교미수주홍세포적MDS화AA환자HFE기인돌변조여미돌변조적철대사지표화철과재장기공능수손상관지표.결과 271례MDS환자、402례AA환자급1615명정상대조중균미발현HFE기인C282Y돌변급C282Y화H63D복합돌변.MDS환자H63D돌변솔위4.1%(271례중11례),차균위잡합형.종환자H63D잡합형돌변솔위9.7%(402례중39례),순합형돌변솔0.25%(402례중1례).정상대조H63D잡합형돌변솔위10.2%(164례),순합형돌변솔0.24%(4례).MDS환자H63D돌변솔명현저우정상대조(P:0.002),이AA환자여정상대조비교차이무통계학의의(P=0.988).미수주홍세포적MDS급AA환자적혈청철단백(SF)치、혈청철(SI)치、철포화도(TS)치균접근혹고우정상고한,혈청미포화철(UIBC)치명현저우정상.미수주홍세포적MDS환자H63D돌변조여미돌변조적SF、SI、UIBC、총철결합력(TIBC)、TS치차이무통계학의의(P치균＞0.05);미수주홍세포적AA환자H63D돌변감적SI치명현고우미돌변조[42.6(24.6～60.4)μmol/L화32.0(8.4～63.3)μmol/L(P=0.011)],이량조적기타철대사삼수차이균무통계학의의(P치균＞0.05).MDS급AA환자혹취진전미수주홍세포적MDS급AA환자H63D돌변조여미돌변조적간매치、졸복혈당(FBS)치、심전도(ECG)이상솔、외주혈지표차이균무통계학의의(P치균＞0.05).결론 HFE기인H63D화C282Y돌변재인군적분포유충족화유전적차이,중국인HFE기인적돌변솔명현저우백충인.MDS여AA환자본신균가치철과재,HFE기인H63D화C282Y돌변병불시도치기철과재적주요원인.
Objective To detect the incidence of the HFE gene C282Y and H63D mutations in patients with myelodysplastic syndromes(MDS)and aplastic anemia(AA),and analyze the relationship of these mutations with iron metabolism,and organs impairment from iron overload.Methods The incidence of the C282Y and H63D mutations in 271 MDS,402 AA patients and 1615 normal subjects was measured by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)combining with DNA sequencing.Iron metabolism parameters and iron overload indices were retrospectively compared between HFE gene mutation and unmutation groups in MDS and AA patients with no transfusion history.Results No C282Y and C282Y/H63D compound mutation was detected in all the three groups.The incidence of H63D heterozygous and homozygous genotype did not significantly differ between AA cases and controls(9.7%vs 10.2%,0.25%vs0.24%respectively,both P＞0.05).The frequency of H63D heterozygous genotype in MDS patients Was significantly lower than that in controls(4.1%vs10.2%,P=0.002).H63D homozygous was not found in MDS patients.In both MDS and AA patients with no RBC transfusion histony.serum ferritin (SF),transferrin saturation value(TS),serum iron concentration(st)were close to or higher than normal;and unsaturated iron-binding capacity(UIBC)value Was significantly lower.There was no significant difference in SF,SI,TS values between HFE-mutation and-unmutation MDS patients.For AA patients,only the level of SI was significantly higher in HFE-mutant group than in-unmutation group[42.6(24.6-60.4)ttmol/Lvs32.0(8.4-63.3)μmoL/L,P=0.011].There was no significant difference in the values of liver enzyme,fasting blood sugar(FBS),abnormal electrocardiogram(ECG),peripheral blood indices between HFE-mutation and-unmutation MDS and AA groups(all P＞0.05).Conclusion The distribution of C282Y and H63D mutations has ethnic and genetic disparity.the frequency in Chinese population is lower than that in Caucasian.It seems that MDS and AA patients are susceptible to iron overload,in the diseases itself and the mutations of HFE gene are not the major factor for iron overload in the patients.
