| Background Essential hypertension (EH) is a kind of syndrome characterized with increasing systemic arterial pressure. Long term hypertension could be an important risk factor in various cardiovascular diseases and be harmful to life and health. The prevalence rate of EH is increasing year by year all around the world. Its mechanism is complicated and unknown up to now. Presently, a majority of scholars have thought EH is a kind of polygenic hereditary disease caused by coactions and/or interaction of genetic and environmental factors. It has obviously genetic heterogeneity.Objective The purpose of this paper is on one hand to discuss the heritability, mode of inheritance and risk factors of EH in Yanbian Korean and Han Chinese populations by epidemiological investigation and on the other hand to detect the single nucleotide polymorphisms (SNPs) of low density lipoprotein receptor (LDLR), adipnectin (apM-1) and proxisome proliferators activated receptor-y2 (PPAR-γ2), furthermore to analyze their haplotypes and allele linkage disequilibrium, and then to study the correlation between the SNPs of LDLR, APM-1 and PPAR-y2 genes and EH, and to sift risk factors and risk haplotypes of EH. This study will provide reliable materials for prevention, diagnosis, treatment and development of new drug of EH in Yanbian Korean and Han Chinese populations, and also benefit the decrease of the morbidity and mortality of EH patients in Yanbian Korean and Han Chinese.Methods (1) Using the basic heredity epidemiology methods and according to the principle of knowing facts and freewill, a total of 280 patients were involved in this study, who had been diagnosed as EH in Yanbian University Hospital and other hospitals in Yanbian, including 152 Korean Chinese and 128 Han Chinese.2105 individuals as first degree relatives were collected. The control group involved 410 healthy individuals, including 227 Korean Chinese and 183 Han Chinese and their 3162 first degree relatives. We filled out the general condition and physical examination by direct face-to-face questionnaires and analyzed detailedly their pedigrees. More than 10 clinical biochemical indicators were detected. Falconer was applied to estimate heritability of EH, and Li-Mantel-Gsrt to determine segregation ratio of EH. The high risk factors of EH were analyzed by unconditional univariate and multivariate logistic regression. (2) The locations of SNPs of LDLR, apM-1 and PPAR-γ2 were found and determined by using the Human SNPs and MapHap database in NCBI. The genotypes and genetic polymorphisms were detected by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and DNA sequencing. Case-contrast analysis was used to investigate the association between genotype frequencies and gene frequencies in 280 EH patients (152 Korean and 128 Han Chinese) and in 410 control subjects (227 Korean and 183 Han Chinese). The haplotype and linkage disequilibrium were analyzed using the SHEsis software on line (http://202.120.7.14/) in order to screen the risk factors of EH.Results (1) The prevalence rates of the EH first-degree relatives were respectively 33.59%and 28.35%in Yanbian Korean and Han Chinese populations, significantly higher than those in control-group which were respectively 13.30%and 12.59%(P< 0.001). Prevalence relative risks (RR) were respectively raised 2.25 and 2.53 times. So the genetic factor is very important in the pathogenesis of EH. It was not significantly different between the prevalence rates of control groups first-degree relatives in Han and Korean Chinese (P>0.05). The total heritability of EH in Yanbian was 59.18%, including 57.02%in Korean Chinese and 60.60%in Han Chinese. There was no statistical difference in EH heritability between Korean and Han Chinese populations (p>0.05). Based on the analysis of the number and prevalence of brethren of proband families, the segregation ratio of EH was 0.18 in Korean Chinese and 0.22 in Han Chinese, corresponding to the characteristics of polygentic hereditary disease (segregation ratio< 0.25), indicating that the EH in Yanbian was polygenic hereditary disease. We can conclude that the important risk factors of EH in Yanbian Korean and Han Chinese populations are family history of hypertension, obesity, drinking and high salt diet by multi-factor logistic regression. (2) The results of the SNPs, haplotype and linkage disequilibrium of LDLR, apM-1 and PPAR-y2 genes were analyzed.10 SNPs were found from LDLR, apM-1 and PPAR-y2 genes in Yanbian Korean and Han Chinese populations by PCR-SSCP and DNA sequencing. They were Asn591Asn (rs1799898), rs5925, rs72658864 and rs72658865 of LDLR gene,-11426 A>G (rsl6861194),-11156insCA(rs60806105),-11377C>G (rs62620185), T45G (Gly15Gly, rs2241766),+349A>G (rs22411767),+276C>A (rs1501299) of apM-1 gene, Prol2Ala (C>G, rs1801282) and C161T (His477His, rs3856806) of PPAR-y2 gene. The genotype frequency and allele frequency accord with the Hardy-Weinberg law, whereas,8 SNPs were not found in this study. They were rs28942086, rs2569548 of LDLR gene,-11391G>A(rs17300539),-11043 C>T (rs76786086), Gly54Val (G162A, rs13061862) of apM-1 gene and Gln438Gln (A>G), Leu481Leu (C>T), Ser457Ser (A>G) of PPAR-y2 gene. The association between the SNPs of LDLR gene and EH in Yanbian Korean and Han Chinese populations were analyzed. In Korean Chinese, the T allele frequency of EH groups and control groups was respectively 11.18%and 20.48%, there was significantly difference between two groups (P<0.01). In Han Chinese, the T allele frequency of EH groups and control groups was respectively 11.33%and 20.77 %, there was significantly difference between two groups (P<0.01) too. There was significantly association in SNPs of the locus rs1799898 of LDLR gene between Korean and Han Chinese populations of Yanbian, but no any statistical difference were found in SNPs of the locus rs5925 of LDLR gene between EH and normal group or between Yanbian Korean and Han Chinese. The association between SNPs of the locus C161T and Pro12Ala of PPAR-y2 gene and EH in Yanbian Korean and Han Chinese populations were analyzed. The genotype frequency of Pro12Ala in PPAR-y2 in Korean EH and control groups were respectively PP:0.951 and 0.949, PA:0.049 and 0.051, there were no any statistical difference (P>0.05). The genotype frequency in Han EH and control groups were respectively PP:0.928 and 0.942, PA:0.072 and 0.058, there were no any statistical difference too (P>0.05). The genotypes and alleles of C161T were not statistical different between EH and normal group or between Yanbian Korean and Han Chinese populations. The association between SNPs of APM-1 gene and EH in Yanbian Korean and Han Chinese populations were analyzed. There was a complete linkage disequilibrium (LD) between-11426A>G and-11156insCA. The frequency of allele-11426G in EH (19.91%) was greater than that in normal group (12.50%) in Yanbian Han Chinese (P<0.05). The SNPs of-11426A>G might be associated with EH in Yanbian Han Chinese. The frequency of allele-11426G in EH and in normal group were respectively 17.42%and 21.10%in Korean Chinese, there was no significant difference. The genotypes and alleles of-11377C>G was not statistical different between EH and normal group or between Yanbian Korean and Han Chinese populations. The genotypes and alleles of T45G,+276G>T and+349A>G was not statistically different between EH and normal group or between Yanbian Korean and Han Chinese populations. The Haplotype frequency of-11426G-11377C of EH was significant higher than that in normal groups in Han Chinese (P<0.05), but there was no significant differerce between EH and normal group in Korean Chinese. The association between joint genotype of Asn591Asn in LDLR,-11426 in APM-1 and His477His in PPAR-y2 and EH was analyzed in Yanbian Han and Korean Chinese populations. There were 20 joint genotypes in three genes. Of them,7 common joint genotypes were found. There was no significant difference between EH and normal group or Korean and Han Chinese (P>0.05).Conclusion (1) EH is a kind of polygenic hereditary disease, Hypertension family medical history, obesity, drinking, higher intake of salt, lower plasma adiponectin were the major risk factors of EH in Yanbian Korean and Han Chinese populations. Preventive measure should be constituted to the people who have risk factors of EH. (2) 10 SNPs were found and analyzed from LDLR, apM-1 and PPAR-γ2 genes in Yanbian Korean and Han Chinese populations. They were Asn591Asn (rs1799898), rs5925, rs72658864 and rs72658865 of LDLR gene;-11426 A>G (rs16861194),-11156insCA(rs60806105),-11377C>G (rs62620185), T45G (Gly15Gly, rs2241766),+349A>G (rs22411767),+276C>A (rs1501299) of apM-1 gene, Pro12Ala (C>G, rs1801282) and C161T (His477His, rs3856806) of PPAR-γ2 gene.8 SNPs were not found in this study. They were rs28942086, rs2569548 of LDLR gene,-11391G>A (rs17300539),-11043C>T (rs76786086), Gly54Val (G162A, rs13061862) of apM-1 gene and Gln438Gln (A>G), Leu481Leu (C>T), Ser457Ser (A>G) of PPAR-γ2 gene. A complete linkage disequilibrium (LD) between-11426A>G and-11156insCA was found for the first time. (3) The SNPs T1773C of LDLR gene might be associated with EH in Yanbian Korean and Han Chinese populations. The allele T1773 might be a risk factor of EH. The SNPs of-11426A>G might be associated with EH in Yanbian Han Chinese. The allele-11426G and haplotype-11426G-11377C of the promoter of adiponectin gene were important risk gene and risk genotype with EH in Yanbian Han Chinese populations. (4) There was no association between the SNPs rs5925 of LDLR gene,+394A>G,+276C>A, T45G and-11377C>G of apM-1 gene and Pro12Ala, C161T of PPAR-γ2 gene and EH in Yanbian Korean and Han Chinese populations. (5) The association between joint genotype of Asn591Asn in LDLR,-11426 in APM-1 and His477His in PPAR-γ2 and EH in Yanbian Korean and Han Chinese populations were not found.
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