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Study On Genetic Susceptibility Of Hypertension In Xinjiang Uygur, Kazak And Han Populations

Posted on:2017-02-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:S Z ChenFull Text:PDF
GTID:1314330485450797Subject:Internal medicine
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Objective:General data and blood samples of Xinjiang Uygur, Kazak and Han hypertensive patients and normotensive controls were acquired through an epidemiological investigation and physical examination. Waist hip ratio (WHR) and body mass index (BMI) were calculated and fasting blood glucose (PFG), blood lipid (TG, TC, LDL-C, HDL-C), blood electrolytes (Na, Cl, K, Ca, Mg) and homocysteine cysteine (Hcy) level were also measured to compared distribution characteristics of the hypertension risk factors in three ethnics.Methods:1. Designed an epidemiology questionnaire, then taken a hypertension epidemiological survey and physical examination in the Uygur, Kazak and Han population which still retains typical ethnic customs and traditional features.2.15ml venous blood was collected in heparin sodium anticoagulated collection tube using vacuum blood sampling device. Centrifugated and collected the supernatant for detection of the fasting plasma glucose (FPG), blood lipid (TG, TC, LDL-C, HDL-C), blood electrolytes (Na, Cl, K, Ca, Mg) and Hcy level. Another 5ml veinal blood in EDTA anticoagulated collection tube was collected for genotype in next step.3. According to the inclusion and exclusion criteria,1244 patients with hypertension were selected including 422 Uygur,425 Kazak and 377 Han; 967 normotensive controls were selected including 339 Uygur,337 Kazak and 291 Han. Fasting plasma glucose (FPG), blood lipid(TG, TC, LDL-C, HDL-C), blood electrolytes(Na, Cl, K, Ca, Mg) and Hcy levels were measured using an automatic biochemical analyzer.Results:1. There were significant differences in age, SBP and DBP between all hypertensive patients and all normotensive controls (P<0.05). The hypertensive patients had higher WHR, BMI, FPG, TG, TC, LDL-C, Na and Hcy levels than normotensive controls after adjusting the variable for the age covariate (P<0.05).2. There were significant differences in age, SBP and DBP between hypertensive patients and normotensive controls in Han population(P<0.05). The hypertensive patients had higher WHR, BMI, FPG, TQ TC, LDL-c, Na, Cl and Hcy levels but lower Ca level than normotensive controls after adjusting the variable for the age covariate (P<0.05).3. There were significant differences in age, SBP and DBP between hypertensive patients and normotensive controls in Kazak population(P<0.05). The hypertensive patients had higher WHR, BMI, FPG, TG, TC, LDL-c, HDL-c, Na and Hcy levels than normotensive controls after adjusting the variable for the age covariate (P<0.05).4. There were significant differences in SBP and DBP between hypertensive patients and normotensive controls in Uygur population(P<0.05). The hypertensive patients had higher WHR, BMI, FPG, TG, TC, LDL-c, Na and Hcy levels but lower HDL-c level than normotensive controls (P<0.05).5. There were significant differences in age and SBP between hypertensive patients of three ethnics (P<0.05). There were significant differences in WHR, BMI, FPG, TG, TC, LDL-c, HDL-c, Na, Cl, K, Ca, Mg and Hcy levels between hypertensive patients of three ethnics after adjusting the variable for the age, SBP and DBP covariate (P<0.05). Kazak hypertensive patients had highest Na, C1 and Hcy levels and lowest WHR, BMI and K levels among hypertensive patients of three ethnics (P<0.05).6. There were significant differences in age, SBP and DBP between normotensive controls of three ethnics (P<0.05). There were significant differences in WHR, BMI, FPG, TG, TC, LDL-c, HDL-c, Na, Cl, K, Ca and Hcy levels between normotensive controls of three ethnics after adjusting the variable for the age and SBP covariate (P<0.05). Kazak normotensive controls had highest Na, Cl and Hcy levels and lowest WHR, BMI and K levels among normotensive controls of three ethnics (P<0.05).Conclusion:1. BMI, WHR, FPG, TG, TC, LDL-c, Na and Hcy were the common influencing factors in the pathogenesis of hypertension in three ethnics. Lower Ca level may play a important role in the pathogenesis of hypertension in the Han but not Uygur and Kazak. HDL-c may play different roles in the pathogenesis of hypertension in three ethnics.2. FPT and blood lipids (TG,TC, LDL-C, HDL-C) metabolism were different each other in the three ethnics. But, Kazak had highest Na, Cl and Hcy levels and lowest WHR, BMI and K levels among either hypertensive patients or normotensive controls of the three ethnics. Compared to the other two ethnic groups, the higher Na, Cl and Hcy levels and lower K level maybe one of the reason that the prevalence rate of Kazak is higher than the other two ethnics.Objective:Studies have shown that NO synthesis was regulated by DDAH/ADMA/ NOS/NO pathway. This study is to explore the correlation between variations in the genes DDAH1 and DDAH2 and hypertension in Xinjiang Kazak, Uygur and Han.Methods:1. We resecquenced the promoter regions and exon regions of DDAH1 and DDAH2 genes in Kazak hypertensive patients to explore the new variations for its highest prevalence rate and chose four polymorphism sites (DDAH1-396 GCGT 4N del/ins, DDAH1rs3087894 C/G, DDAH2 rs9267551 C/G and DDAH2 rs805304 A/C) as the target polymorphisms.2. According to the inclusion and exclusion criteria,1244 patients with hypertension were selected including 422 Uygur,425 Kazak and 377 Han; 967 normotensive controls were selected including 339 Uygur,337 Kazak and 291 Han (same to the first part). Genomic DNA of all samples were extracted for genotype.3. We conducted a case-control study in three ethnics (Uygur, Kazak and Han) to systemically investigate associations between DDAH1-396 GCGT 4N del/ins, DDAH1 rs3087894 C/G, DDAH2 rs9267551 C/G, DDAH2 rs805304 A/C polymorphisms and hypertension in dominant model, co-dominant model and recessive model. The polymorphism sites were genotyped using the TaqMan nuclease assay.Results:1. Nine polymorphisms were found in resecquencing of the promoter region and exon regions of DDAH1. Seven of them were reported including DDAH1-396 GCGT 4N ins/del, rs2076699 A/G, rs2230820 A/G, rs1498373 G/T, rs1498374 A/G, rs1498375 A/T and rs3087894 C/G.The minor allele frequences were 0.09,0.23,0.12,0.34,0.10,0.31 and 0.27 respectively. Two of them were unreported including chr1:85816153 C>G (GRCh37/hg19) and DDAH1 chrl:85787197 G>A (GRCh37/hg19). The minor allele frequences were 0.02 and 0.01 respectively.2. Five polymorphisms were found in resecquencing of the promoter region and exon region of DDAH2. Four of them were reported including DDAH2 rs805304 A/C, DDAH2 rs9267551 C/G, DDAH2 rs11540321 A/G and DDAH2 rs28366162 C/T polymorphisms. The minor allele frequences were 0.48,0.07,0.04 and 0.02 respectively. DDAH2 chr6: 31695437 C>T (GRCh37/hg19) was unreported. The minor allele frequence was 0.01.3. The genotype distribution of the four polymorphisms including DDAH1-396 GCGT 4N del/ins, rs3087894 C/G, DDAH2 rs9267551 C/G and rs805304 A/C was in line with the Hardy-Weinberg equilibrium (P>0.05). The genotype distribution of four polymorphisms except for DDAH2 rs805304 A/C were significantly different in the three ethnics (P< 0.05).4.The results showed that the four polymorphisms were not significantly different between all hypertension patients and all controls, irrespective of the ethnic factor (P>0.05). Then, we assessed the effect of gene polymorphisms on hypertension in an ethnicity-specific case-control analysis. No significant difference was observed in DDAH1-396 GCGT 4N del/ins, DDAH2 rs9267551 C/G and rs805304 A/C polymorphisms (P>0.05). The C-allele of rs3087894 in DDAH1 was a risk factor for hypertension in the Kazak in the dominant model and co-dominant model(P< 0.05). In contrast, the C-allele of rs3087894 polymorphism seemed to be a protective factor against hypertension in the Uygur in the recessive model (P<0.05). Similar findings for rs3087894 C/G polymorphism were also observed after adjusting the variable for the age covariate. Whereas there were no differences between patients and controls in the Han (P>0.05).Conclusion:Our results indicated that the C-allele of rs3087894 polymorphism in DDAH1 was a risk factor for hypertension in the Kazak but a protective factor in the Uygur.Objective:Studies have shown that the CAMKIV rs10491334 C/T polymorphism and CTSL rs3118869 A/C polymorphism were associated with hypertension. This study is to explore the correlation between the two polymorphisms and hypertension in Xinjiang Kazak, Uygur and Han.Methods:1. According to the inclusion and exclusion criteria,1244 patients with hypertension were selected including 422 Uygur,425 Kazak and 377 Han; 967 normotensive controls were selected including 339 Uygur,337 Kazak and 291 Han (same to the first part and the second part). Genomic DNA of all samples were extracted for genotype.2. We conducted a case-control study in three ethnics (Uygur, Kazak and Han) to systemically investigate associations between CAMK?rs10491334 C/T, CTSL rs3118869 A/C polymorphisms and hypertension in dominant model, co-dominant model and recessive model. The polymorphism sites were genotyped using the TaqMan nuclease assay.Results:1. The genotype distribution of CAMKIV rs 10491334 C/T polymorphism was in line with the Hardy-Weinberg equilibrium (P>0.05). The genotype distribution of CAMKIV rs10491334 C/T polymorphism was significantly different in the three ethnics(P <0.05).2. The results showed that the CAMK? rs10491334 C/T polymorphism was not significantly different between all hypertension patients and all controls, irrespective of the ethnic factor (P>0.05). Then, we assessed the effect of gene polymorphisms on hypertension in an ethnicity-specific case-control analysis. The T-allele of CaMK? rs10491334 was a risk factor for hypertension in the dominant model in the Uygur (P< 0.05). The T-allele frequency in patients with hypertension was twice that of the controls (12.5% vs.6.38%). However, there were no significant differences in the other two ethnics.3. The genotype distribution of CTSL rs3118869 A/C polymorphism was in line with the Hardy-Weinberg equilibrium (P>0.05). The genotype distribution of CTSL rs3118869 A/C polymorphism was not significantly different in the three ethnics (P>0.05).4. The results showed that the CTSL rs3118869 A/C polymorphism was not significantly different between hypertension patients and controls in three ethnics separately when we assessed the effect of gene polymorphisms on hypertension in an ethnicity-specific case-control analysis(P>0.05). But, the results showed that the CTSL rs3118869 A/C polymorphism was significantly different in co-dominant modle and recessive modle between all hypertension patients and all controls, irrespective of the ethnic factor(P<0.05). Similar findings for CTSL rs3118869 A/C polymorphism were also observed in recessive modle after adjusting the variable for the age covariate(P<0.05). The A-allele of CTSL rs3118869 polymorphism was a protective factor for hypertension.Conclusion:1. The T-allele of CaMK? rs10491334 polymorphism was a risk factor for hypertension in the Uygur.2. The A-allele of CTSL rs3118869 polymorphism was a protective factor for hypertension.
Keywords/Search Tags:hypertension, fasting plasma glucose, blood lipid, blood electrolytes, homocysteine cysteine, DDAH1, DDAH2, polymorphism, CAMK?, CTSL
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