CETP polymorphisms confer genetic contribution to centenarians of Hainan, south of China

OBJECTIVE@#In this paper, we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island.@*METHODS@#We tested the TaqIB and I405V polymorphisms of CETP gene among 276 centenarians and 301 matched healthy individuals by AS-PCR and analyzed the data with SPSS software package (Version 19.0).@*RESULTS@#Our data indicated that allele B1 and V have the significant differences between centenarians and healthy control groups with P < 0.001. Further analysis implied that genotypes B1B1 (P < 0.001, OR = 0.148, 95% CI = 0.095-0.230) and VV (P < 0.001 and OR = 0.353, 95% CI = 0.237-0.525) were significantly different between centenarians and matched controls. The combination of B and V, such as B1B1-II (P < 0.001, OR = 0.128, 95% CI = 0.049-0.329), B1B1-IV (P < 0.001, OR = 0.115, 95% CI = 0.056-0.237), B1B2-VV (P < 0.05, OR = 0.534, 95% CI = 0.310-0.920), and B2B2-VV (P < 0.001, OR = 0.198, 95% CI = 0.086-0.453) have significant differences between centenarians and matched healthy individuals from Hainan.@*CONCLUSION@#Our results implied that allele B1B1 and VV, as well as the combination B1B1-II, B1B1-IV, B1B2-VV and B2B2-VV may contribute to the longevity in centenarians of Hainan, south of China.

CETP polymorphisms confer genetic contribution to centenarians of Hainan, south of China

Objective In this paper, we will discuss if the CETP polymorphism contributes to the centenarians in Hainan island. Methods We tested the TaqIB and I405V polymorphisms of CETP gene among 276 centenarians and 301 matched healthy individuals by AS-PCR and analyzed the data with SPSS software package (Version 19.0). Results Our data indicated that allele B1 and V have the significant differences between centenarians and healthy control groups with P < 0.001. Further analysis implied that genotypes B1B1 (P < 0.001, OR = 0.148, 95% CI = 0.095-0.230) and VV (P < 0.001 and OR = 0.353, 95% CI = 0.237-0.525) were significantly different between centenarians and matched controls. The combination of B and V, such as B1B1-II (P < 0.001, OR = 0.128, 95% CI = 0.049-0.329), B1B1-IV (P < 0.001, OR = 0.115, 95% CI = 0.056-0.237), B1B2-VV (P < 0.05, OR = 0.534, 95% CI = 0.310-0.920), and B2B2-VV (P < 0.001, OR = 0.198, 95% CI = 0.086-0.453) have significant differences between centenarians and matched healthy individuals from Hainan. Conclusion Our results implied that allele B1B1 and VV, as well as the combination B1B1-II, B1B1-IV, B1B2-VV and B2B2-VV may contribute to the longevity in centenarians of Hainan, south of China.

Correlation between the Xba I polymorphism of apoB gene and serum lipid profiles in Li ethnic group

OBJECTIVE@#To study correlation between the Xba I polymorphism of apoB gene and plasma lipid profiles in Li ethnic group.@*METHODS@#Total 151 cases of healthy Li people were recruited randomly by cluster sampling and 200 Han people were recruited as control; blood was drawn to analyze Xba I polymorphism distribution of apoB gene and serum lipid levels.@*RESULTS@#There were lower serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in serum of Li people; while, high density lipoprotein cholesterol (HDL-C), X-/X+ genotype and X+ allele frequencies exhibited higher levels than Han people. Interestingly, HDL-C level was reduced, while LDL-C level was enhanced in subjects carrying heterozygous (X-/X+) genotype compared to homozygous (X-/X-) genotype. Additionally, there were no difference in serum level of triglyceride, TC, apoprotein A (apo A) and apoprotein B (apo B) between Li and Han people, the same results were showed between X-/X+ and X-/X- genotype carriers.@*CONCLUSIONS@#Xba I polymorphism of apoB gene is correlated to the profiles of serum lipid level, X-/X+ genotype carriers are phenotyped with higher LDL-C level and lower level of HDL-C in Li ethnic group.

Identification of a novel large deletion of factor subunit A mRNA associated with hereditary factor deficiency / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the expressed mRNA of the factor subunit A (FA) in monocyte in a hereditary factor (F) deficiency family.</p><p><b>METHODS</b>The F A mRNA of the proband and the other family members was analyzed by RT-PCR, semi-quantitative RT-PCR, cloning and sequencing. The three dimensional structure of the protein was predicted by SWISS-MODEL and viewed by RASMIOL.</p><p><b>RESULTS</b>(1) A large in frame deletion from codons 11 to 279, spanning from exon 2 to 7 of F A (DelCD11-279), was identified in the proband at mRNA level and a truncated protein is predicted composed of 464 amino acids. Compared with the normal and the other families, the proband showed lower level of F A mRNA in RT-PCR. (2) SWISS-MODEL analysis showed that the truncated protein lacked the β-sandwich and a part of catalytic core, resulting in loss of the normal catalytic domains.</p><p><b>CONCLUSION</b>DelCD11-279 of F A mRNA is associated with hereditary F deficiency. The reduced expressing level of F A gene is one of the causes resulting in F deficiency in the patients.</p>

Molecular characterization of 71 cases of glucose-6-phosphate dehydrogenase deficiency in Hainan province / 中华血液学杂志

<p><b>OBJECTIVE</b>To molecularly analyze in Han and Li individuals of glucose-6-phosphate dehydrogenase deficiency in Hainan, China.</p><p><b>METHODS</b>The amplification refractory mutation system (ARMS) was employed to detect G1376T, G1388A and A95G mutations. The coding regions and flanking intronic regions from the second to the thirteenth exons of G6PD gene was analyzed by DNA sequencing to characterize the gene mutations in samples without G1376T, G1388A and A95G mutations.</p><p><b>RESULTS</b>Among 29 Han cases of G6PD deficiency, 11 had G1376T (37.9%), 2 G1388A (6.9%), 1 G1376T and G1388A (3.4%) and 1 G1376T and A95G (3.4%) were identified. Mutations of G1376T, G1388A, A95G and their complex accounted for 51.7% of G6PD deficiency in the Han individuals. Among 42 Li cases of G6PD deficiency, 25 had G1376T (59.5%), 6 G1388A (14.3%), 2 A95G (4.8%), 4 G1376T and G1388A (9.5%), 1 G1376T and A95G (2.4% )were identified. These mutations accounted for 90.5% of the Li individuals. Gene mutation of 18 cases (14 Han and 4 Li individuals) remained unknown. Sequencing results of the 18 samples indicated that one case had a single base of T deletion at nucleotide 636 or 637 in the 5th intron (IVS-5 636 or 637 T del) and two cases had C1311T with IVS-11 T93C mutation.</p><p><b>CONCLUSION</b>G6PD G1376T and G1388A are the most common mutations in the populations of the Han and Li nationalities in Hainan. The IVS-5 636 or 637 T del mutation is first reported in Chinese, and the complex mutation of G1376T/A95G is first found in the Li nationality.</p>

A related analysis for alpha, beta fibrinogen gene haplotypes and nucleotide polymorphisms associated with the ischemic stroke in Hainan Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the association of that the polymorphisms and haplotypes of Taq I site in beta fibrinogen gene and the single nucleotide sites -455 G/A, -249 C/T, -148 C/T, +1689T/G, Bsm A I G/C, 448 G/A, Bcl I G/A, Hinf I A/C in beta-fibrinogen gene are linked up with the ischemic stroke(IS).</p><p><b>METHODS</b>Turbidmetric assay was used to measure the plasma fibrinogen level of one hundred and sixty cases with ischemic stroke and one hundred and thirty healthy individuals from Hainanese Han population. The polymorphisms and genotypes were characterized by PCR-RFLP. Hardy-Weinberg equilibrium and statistical differences of allelic, genotype and haplotype frequencies were obtained by Chi-square test. Pairwise linkage disequilibrium was calculated and haplotypes of nine or four polymorphisms were estimated by the EH + program.</p><p><b>RESULTS</b>There were highly significant differences in genotype frequencies and allelic frequencies of the polymorphisms -455 G/A, -148 C/T, 448 G/A, which happened between the IS group and control subjects (P< 0.01). However, the significant differences of the allelic frequencies in the other six polymorphisms were not found between the IS group and the control (P> 0.05). The odds ratio(OR) with the rare alleles of A -455, T -148 and A 448 is 2.46, 2.30 and 2.08 (95% confidence interval 1.153%-3.924%, 1.429%-3.694% and 1.298%-3.329%) respectively. No definite haplotype block was found by linkage disequilibrium analysis in the control group and the IS group. Association of haplotypes constructed from the nine polymorphisms with IS was not found. Among the haplotypes constructed from four polymorphisms including -455 G/A, -148 C/T, 448 G/A alleles, haplotype differences were found between the control group and the IS group. Haplotypes with G -455, C -148, G448 alleles appeared more frequently in control group(P< or = 0.01), whereas haplotypes with A -455, T -148, A 448 occurred more frequently in the IS group(P< 0.01).</p><p><b>CONCLUSION</b>The results of multi-allele and haplotype analysis indicated that the polymorphisms -455 G/A, -148 C/T, 448 G/A in beta fibrinogen gene were the possible risk factors associated with the occurrence of ischemic stroke in Hainan Han population.</p>

Association of fibrinogen B beta -1420G/A, -993C/T and -854G/A gene polymorphism with coronary heart disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the frequency of FGB gene -1420G/A, -993C/T and -854G/A polymorphisms, and their association with plasma fibrinogen levels in patients with coronary heart disease and in health adults.</p><p><b>METHODS</b>The FGB gene -1420G/A, -993C/T and -854G/A polymorphisms were analyzed with restriction fragment length polymorphisms, polymerase chain reaction with allele-specific primer and nucleotide sequencing methods. Plasma fibrinogen levels were determined by turbidimetry.</p><p><b>RESULTS</b>The frequencies of -1420A were 0.33 in patients with coronary heart disease and 0.26 in health adults. The frequencies of -1420A in coronary heart disease were apparently higher than that in health adults. There were no difference in frequencies of other two alleles. The logistic study suggested -1420G/A polymorphism was associated with coronary heart disease. There are significantly difference in plasma fibrinogen levels in two groups. Plasma fibrinogen levels were significantly increased in patients with coronary heart disease.</p><p><b>CONCLUSION</b>This study suggests -1420G/A polymorphism may be associated with occurrence of coronary heart disease.</p>

Nine polymorphisms of fibrinogen gene and their association with plasma fibrinogen levels in Hainan Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the allelic frequencies of polymorphisms of alpha Taq I and beta Bcl I, Hinf I A/C, 448 G/A, beta BsmA I G/C, +1689T/G, -148C/T, -249C/T, -455G/A in Hainan Han population and their association with plasma fibrinogen level.</p><p><b>METHODS</b>Turbidmetric assay was used to measure plasma fibrinogen level of two hundred and thirty-eight healthy individuals. The genotypes were characterized by PCR-RFLP and sequence analysis. The relationships between the genotypes and plasma fibrinogen levels were analyzed by t test and ANOVA.</p><p><b>RESULTS</b>The frequencies of the rare alleles of alpha Taq I and beta Bcl I, Hinf I A/C, 448 G/A, beta BsmA I G/C, +1689T/G, -148C/T, -249C/T, -455G/A polymorphisms were 0.445, 0.239, 0.134, 0.235, 0.273, 0.241, 0.265, 0.441, 0.254 respectively. In the general population, the plasma fibrinogen level is significantly higher in the groups of genotypes -455GA and AA, -148CT and TT, alpha Taq I T1T1 than in the group of wild types(P=0.004, 0.015 and 0.043 respectively). In the men, plasma fibrinogen level is significantly higher in the groups of genotypes -455GA and AA, -148CT and TT, alpha Taq I T1T1, alpha Taq I T1T2 than in the group of wild types(P=0.001, 0.023, 0.003 and 0.032 respectively). In the women, no significant genotype association with plasma fibrinogen level was detected.</p><p><b>CONCLUSION</b>There was linkage disequilibrium between the fibrinogen gene loci. The beta -455G/A beta 448G/A, alpha Fg Taq I polymorphisms were associated with the difference in plasma fibrinogen in men. A(-455), T(-148) and alpha Taq I T1 alleles were associated with higher fibrinogen levels.</p>

Effect of beta-Fibrinogen-455 Gene Polymorphism on Plasma Fibrinogen Levels in Patients with Ischemic Stroke / 中国实验血液学杂志

In large prospective studies, plasma fibrinogen levels have been shown to be an independent risk factor of vascular disease, including ischemic stroke. Elevated plasma fibrinogen in an individual could be due to the presence of predisposing genetic and/or environmental factors, such as smoking. Of the polymorphisms studies to date, the beta-fibrinogen-455 (beta-Fg-455) G-->A substitution in the 5' flanking region is associated with the most consistent difference in plasma fibrinogen levels in both case-control studies and in selected groups of healthy individuals. In order to further elucidate the role of the beta-Fg-455 G-->A substitution in determining fibrinogen levels and susceptibility to ischemic stroke in case-control population, including 104 individuals with verified ischemic stroke and 156 healthy individuals. Turbidimetriy assays were used to measure plasma fibrinogen levels of all samples. The beta-Fg-455 G-->A mutation was identified by the polymerase chain reaction followed by restriction enzyme digestion of the amplified DNA with HaeIII. The plasma fibrinogen level in patients with ischemic stroke [(3.51 +/- 1.09) g/L] was significantly higher than that in the control [(3.08 +/- 0.71) g/L] (P < 0.01). The A-allele is associated with elevated fibrinogen levels in both patients and controls. The plasma fibrinogen levels in controls with A-allele in elder people were higher than in younger people (P < 0.05). Those with A allele in males of ischemic stroke had significantly higher plasma fibrinogen levels in smokers than in non-smokers and ex-smokers (P < 0.05), but it was not significantly difference in subjects of GG genotype (P > 0.05). Our data demonstrates an association of the beta-Fg promoter A-455 allele with higher fibrinogen levels in the general population, and suggests that the A-allele may be a susceptible predictor of ischemic stroke, particularly in aging and smoking.