CAJ | 학술논문

目的分析参与血管发育的转化生长因子-β1( TGF-β1)受体2(TGFBR2)基因启动子区的遗传变异与中国汉族人群高血压的关系.方法研究对象选自 2009年江苏省宜兴市两个乡镇社区高血压整群抽样调查人群.高血压病例2012例,按年龄(±2岁)、性别匹配选择健康对照2116名;收集流行病学资料和体格检查资料并检测血糖、血脂等临床生化指标.基因位点选择采用连锁不平衡分析的方法,选取TGFBR2基因5 ' 上游启动子的2个标签单核苷酸多态性(tagSNP) (rs6785358,-3779 A/G;rs764522,-1444 C/G)进行基因分型和关联分析.结果 rs6785358位点AA、AG、GG基因型频数在病例组中为1455(72.3％)、517(25.7％)、40(2.0％),在对照组中为1582(74.8％)、490(23.2％)、43(2.0％);rs764522位点CC、CG、GG基因型频数在病例组中为1524(75.7％)、464(23.1％)、24(1.2％),在对照组中为1654(78.2％)、436( 20.6％)、26(1.2％).校正年龄、性别、血糖、血脂、吸烟与饮酒等混杂因素后,rs764522 位点显性模型与高血压关联有统计学意义[ 0R(95％ CI)值为1.17(1.01 ～1.36),P＜0.05].按年龄、性别、吸烟、饮酒等因素进行分层分析结果显示,在≥55岁人群中,携带rs764522突变G等位基因型(CG+ GG)者高血压患病风险增加[OR(95％ CI)值为1.21(1.01 ～1.45),P＜0.05].而rs6785358位点基因型、等位基因型与高血压的关联均无统计学意义(P＞0.05);单体型基因分析结果未发现rs764522与rs6785358位点存在联合作用(P＞0.05).不同基因型之间血压水平比较也未发现上述两个SNP变异与血压数量性状存在关联(P＞0.05).结论 TGFBR2基因rs764522位点与高年龄人群高血压患病风险增加有关.
목적 분석삼여혈관발육적전화생장인자-β1( TGF-β1)수체2(TGFBR2)기인계동자구적유전변이여중국한족인군고혈압적관계.방법 연구대상선자 2009년강소성의흥시량개향진사구고혈압정군추양조사인군.고혈압병례2012례,안년령(±2세)、성별필배선택건강대조2116명;수집류행병학자료화체격검사자료병검측혈당、혈지등림상생화지표.기인위점선택채용련쇄불평형분석적방법,선취TGFBR2기인5 ' 상유계동자적2개표첨단핵감산다태성(tagSNP) (rs6785358,-3779 A/G;rs764522,-1444 C/G)진행기인분형화관련분석.결과 rs6785358위점AA、AG、GG기인형빈수재병례조중위1455(72.3％)、517(25.7％)、40(2.0％),재대조조중위1582(74.8％)、490(23.2％)、43(2.0％);rs764522위점CC、CG、GG기인형빈수재병례조중위1524(75.7％)、464(23.1％)、24(1.2％),재대조조중위1654(78.2％)、436( 20.6％)、26(1.2％).교정년령、성별、혈당、혈지、흡연여음주등혼잡인소후,rs764522 위점현성모형여고혈압관련유통계학의의[ 0R(95％ CI)치위1.17(1.01 ～1.36),P＜0.05].안년령、성별、흡연、음주등인소진행분층분석결과현시,재≥55세인군중,휴대rs764522돌변G등위기인형(CG+ GG)자고혈압환병풍험증가[OR(95％ CI)치위1.21(1.01 ～1.45),P＜0.05].이rs6785358위점기인형、등위기인형여고혈압적관련균무통계학의의(P＞0.05);단체형기인분석결과미발현rs764522여rs6785358위점존재연합작용(P＞0.05).불동기인형지간혈압수평비교야미발현상술량개SNP변이여혈압수량성상존재관련(P＞0.05).결론 TGFBR2기인rs764522위점여고년령인군고혈압환병풍험증가유관.
Objective To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-β1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population.Methods The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city,Jiangsu province in 2009.Overall,2012patients with hypertension and 2116 age ( ± 2 years ) and sex-matched unrelated controls were selected.Epidemiological data,physical measurements results and serum glucose and lipid biomarker were collected and detected.Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms ( tagSNP ) in 5' upstream of TGFBR2 gene ( rs6785358,-3779A/G; rs764522,-1444C/G) were selected for genotyping and analyzing for the association with hypertension.Results The frequencies of AA,AG,GG in case and control of rs6785358 were 1455 (72.3％),517 (25.7％),40(2.0％) and 1582(74.8％),490(23.2％),43(2.0％) respectively,and CC,CG,GG of rs764522were 1524(75.7％),464(23.1％),24(1.2％) and 1654(78.2％),436(20.6％),26(1.2％)respectively.SNP rs764522 was significantly associated with EH and OR (95％ CI) were 1.17 ( 1.01-1.36)(P ＜ 0.05 )in dominant model after adjustment for confounding factors such as age,sex,glucose,lipids,smoking and alcohol drinking.Further stratification analysis by age,sex,smoking and alcohol driuking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype ( OR =1.21,95％ CI:1.01 -1.45 ) ( P ＜ 0.05 ) in ≥ 55 years group.No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P ＞ 0.05 ).Haplotype analysis showed thai no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls ( P ＞ 0.05),and no significant blood pressure change was found between genotype variations of rs6785358and rs764522(P ＞0.05).Conclusion SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.