中华糖尿病杂志
中華糖尿病雜誌
중화당뇨병잡지
CHINES JOURNAL OF DLABETES MELLITUS
2012年
8期
483-487
,共5页
糖尿病,1型%人类白细胞抗原%等位基因%单倍型%多态性,单核苷酸%连锁不平衡
糖尿病,1型%人類白細胞抗原%等位基因%單倍型%多態性,單覈苷痠%連鎖不平衡
당뇨병,1형%인류백세포항원%등위기인%단배형%다태성,단핵감산%련쇄불평형
Diabetes mellitus,type 1%Human leukocyte antigens%Alleles%Haplotypes%Polymorphism,single nucleotide%Linkage disequilibrium
目的 研究江苏地区人类白细胞抗原( HLA )-A和HLA-DRB1基因频率及单倍型与1型糖尿病的相关性.方法 于2008至2009年在江苏省江阴市和南京市选择白发酮症急性起病、依赖胰岛素治疗的1型糖尿病门诊或住院患者51例(1型糖尿病组),其中男27例,女24例,平均发病年龄(14±9)岁.另以2002至2006年登记加入中华骨髓库江苏分库的汉族无关骨髓捐献志愿者HLA分型资料20 248份为对照.从受试者外周血中提取细胞基因组DNA,利用聚合酶链反应-寡核苷酸探针序列特异性引物技术进行HLA-A和HLA-DRB1基因分型,应用Arlequin软件分析计算单倍型频率及连锁不平衡情况,通过卡方检验等比较组间基因频率、单倍型频率及疾病相关性分析.结果 HLA-A位点频率最高的为A*02和A*24,HLA-DRB1位点频率最高的为DRB1* 09.与对照组相比,1型糖尿病组HLA-A* 03[6.86％ (7/102)比2.43％(984/40 496), x2=8.40,P＜0.01,比值比(OR)=3.00]、A*24[27.45％(28/102)比16.79％(6799/40496),x2 =8.27,P＜0.01,OR=1.87]和DRB1*09[32.35％ (33/102)比16.15％ (6540/40 496),x2=19.69,P＜0.01,OR=2.47]、DRB1*03[15.69％(16/102)比4.76％(1927/40 496),x2=26.66,P＜0.01,OR =3.69]频率显著升高.A*01-DRB1* 03在连锁不平衡分析中为1型糖尿病组所特有.结论 检测出位点A*03、A*24及DR03、DR09对1型糖尿病的易患性,发现3个有易患作用的A-DR单倍型,观察到与1型糖尿病关联的祖先单倍型A01DR03.
目的 研究江囌地區人類白細胞抗原( HLA )-A和HLA-DRB1基因頻率及單倍型與1型糖尿病的相關性.方法 于2008至2009年在江囌省江陰市和南京市選擇白髮酮癥急性起病、依賴胰島素治療的1型糖尿病門診或住院患者51例(1型糖尿病組),其中男27例,女24例,平均髮病年齡(14±9)歲.另以2002至2006年登記加入中華骨髓庫江囌分庫的漢族無關骨髓捐獻誌願者HLA分型資料20 248份為對照.從受試者外週血中提取細胞基因組DNA,利用聚閤酶鏈反應-寡覈苷痠探針序列特異性引物技術進行HLA-A和HLA-DRB1基因分型,應用Arlequin軟件分析計算單倍型頻率及連鎖不平衡情況,通過卡方檢驗等比較組間基因頻率、單倍型頻率及疾病相關性分析.結果 HLA-A位點頻率最高的為A*02和A*24,HLA-DRB1位點頻率最高的為DRB1* 09.與對照組相比,1型糖尿病組HLA-A* 03[6.86％ (7/102)比2.43％(984/40 496), x2=8.40,P＜0.01,比值比(OR)=3.00]、A*24[27.45％(28/102)比16.79％(6799/40496),x2 =8.27,P＜0.01,OR=1.87]和DRB1*09[32.35％ (33/102)比16.15％ (6540/40 496),x2=19.69,P＜0.01,OR=2.47]、DRB1*03[15.69％(16/102)比4.76％(1927/40 496),x2=26.66,P＜0.01,OR =3.69]頻率顯著升高.A*01-DRB1* 03在連鎖不平衡分析中為1型糖尿病組所特有.結論 檢測齣位點A*03、A*24及DR03、DR09對1型糖尿病的易患性,髮現3箇有易患作用的A-DR單倍型,觀察到與1型糖尿病關聯的祖先單倍型A01DR03.
목적 연구강소지구인류백세포항원( HLA )-A화HLA-DRB1기인빈솔급단배형여1형당뇨병적상관성.방법 우2008지2009년재강소성강음시화남경시선택백발동증급성기병、의뢰이도소치료적1형당뇨병문진혹주원환자51례(1형당뇨병조),기중남27례,녀24례,평균발병년령(14±9)세.령이2002지2006년등기가입중화골수고강소분고적한족무관골수연헌지원자HLA분형자료20 248빈위대조.종수시자외주혈중제취세포기인조DNA,이용취합매련반응-과핵감산탐침서렬특이성인물기술진행HLA-A화HLA-DRB1기인분형,응용Arlequin연건분석계산단배형빈솔급련쇄불평형정황,통과잡방검험등비교조간기인빈솔、단배형빈솔급질병상관성분석.결과 HLA-A위점빈솔최고적위A*02화A*24,HLA-DRB1위점빈솔최고적위DRB1* 09.여대조조상비,1형당뇨병조HLA-A* 03[6.86％ (7/102)비2.43％(984/40 496), x2=8.40,P＜0.01,비치비(OR)=3.00]、A*24[27.45％(28/102)비16.79％(6799/40496),x2 =8.27,P＜0.01,OR=1.87]화DRB1*09[32.35％ (33/102)비16.15％ (6540/40 496),x2=19.69,P＜0.01,OR=2.47]、DRB1*03[15.69％(16/102)비4.76％(1927/40 496),x2=26.66,P＜0.01,OR =3.69]빈솔현저승고.A*01-DRB1* 03재련쇄불평형분석중위1형당뇨병조소특유.결론 검측출위점A*03、A*24급DR03、DR09대1형당뇨병적역환성,발현3개유역환작용적A-DR단배형,관찰도여1형당뇨병관련적조선단배형A01DR03.
Objective To investigate the relationship between type 1 diabetes mellitus and human leukocyte antigen(HLA)-A and-DRB1 gene frequencies and haplotypes.Methods Fifty-one patients (male 27,female 24,average age of onset ( 14 ± 9) y) with spontaneously acute ketotic onset and insulindependent type 1 diabetes mellitus (T1DM) were enrolled during 2008 and 2009 from Jiangyin and Nanjing city in Jiangsu Province.HLA typing data with the similar genetic background of 20 248 unrelated donors in Jiangsu Branch of Chinese Marrow Donor Program were set as controls. DNA was extracted from the peripheral blood,and HLA-A or DRBI gene was genotyped with polymerase chain reaction-sequence specific oligonucleotide primers,and the haplotype frequencies,linkage disequilibrium and correlation with type 1 diabetes were also analyzed bv Arlequin software and Chi-square test in the two groups. Results The frequencies of A * 02 and A * 24 were the highest in HLA-A locus,and DRB1 * 09 was the highest in DRB1 locus.Compared with the controlled group,the frequencies of HLA-A * 03,HLA-A * 24,DRB1 * 09 and DRB1 * 03 were significantly increased in T(l)DM patients(6.86％ vs 2.43％,27.45％ vs 16.79％,32.35％vs 16.15％,15.69％ vs 4.76％,respectively;x2 =8.40,8.27,19.69,26.66;odds ratio =3.00,1.87,2.47,3.69;all P ＜ 0.01 ). A * 01-DRB1 * 03 haplotype was specific with T1DM group in linkage disequilibrium analysis.Conclusion We find the herd susceptibility of loci A * 03,A * 24 and DR03,DR09 in T1DM subjects,and three A-DR susceptibility haplotypes. The relationship between ancestor haplotype of A01DR03 and T1DM is confirmed.
