Apolipoprotein E polymorphism in the Indian and Mestizo populations of Mexico

Apolipoprotein E (APOE) genotypes were determined in 75 Mazatecan Indians and 83 Mexican mestizos. APOE allele and genotype frequencies in Mazatecans and mestizos were similar, with high frequencies of the APOE*3 allele (0.900 and 0.915, respectively) and the E3/3 genotype (0.813 and 0.831, respectively) and an absence in both samples of the APOE*2 allele. Our data are similar to those previously described for Mexican-American and Mayan populations, which show the highest frequency worldwide of the APOE*3 allele and the E3/3 genotype. Mazatecans and mestizos also show a decreased frequency of the APOE*4 allele when compared to other Amerindian groups. The absence of the APOE*2 allele has also been reported in other Amerindian groups such as Mayans and Cayapa, whereas in Caucasians the average frequency of this allele is about 8%. Our data are in agreement with previous reports showing absence of the APOE*2 allele in Native American groups. These findings suggest that the APOE*2 allele was absent in humans from northern Asia who settled in the Arctic and populated the American continent.     

Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population

Within the past few years there has been increasing evidence that the genetic variation in the genes coding pro- and anti-inflammatory markers may play an important role in the pathogenesis of various human diseases, including stroke. The aim of the study was to evaluate the association of Interleukin-10 (IL-10)-1082 G/A, promoter polymorphism (rs1800896) with ischemic stroke in a South Indian population from Andhra Pradesh. In this study 480 ischemic stroke patients and 470 age and sex matched healthy controls were included. The ischemic stroke patients were classified according to TOAST classification. The region of interest in the IL-10 gene was amplified by polymerase chain reaction with the use of allele specific oligonucleotide primers flanking the polymorphic region. Association between genotypes and stroke was examined by Odds Ratio (OR) with 95% confidence interval (CI) and Chi-square analysis. Significant difference was observed between the patients and healthy controls, in genotypic distribution as well as allelic frequency (p < 0.05). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and IL-10 gene variant revealed that -1082 G/A polymorphism in the promoter region of IL-10 gene is significantly [adjusted OR = 2.26; 95% C.I. (1.24–4.15), p < 0.001] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We found significant association of this polymorphism with stroke of undetermined etiology (p < 0.001). Moreover, hypertensive and diabetic individuals bearing A allele of IL-10 gene in high frequency were found to be more predisposed to stroke.     

Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population

Within the past few years there has been increasing evidence that the genetic variation in the genes coding pro- and anti-inflammatory markers may play an important role in the pathogenesis of various human diseases, including stroke. The aim of the study was to evaluate the association of Interleukin-10 (IL-10)-1082 G/A, promoter polymorphism (rs1800896) with ischemic stroke in a South Indian population from Andhra Pradesh. In this study 480 ischemic stroke patients and 470 age and sex matched healthy controls were included. The ischemic stroke patients were classified according to TOAST classification. The region of interest in the IL-10 gene was amplified by polymerase chain reaction with the use of allele specific oligonucleotide primers flanking the polymorphic region. Association between genotypes and stroke was examined by Odds Ratio (OR) with 95% confidence interval (CI) and Chi-square analysis. Significant difference was observed between the patients and healthy controls, in genotypic distribution as well as allelic frequency (p<0.05). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and IL-10 gene variant revealed that -1082 G/A polymorphism in the promoter region of IL-10 gene is significantly [adjusted OR=2.26; 95% C.I. (1.24-4.15), p<0.001] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We found significant association of this polymorphism with stroke of undetermined etiology (p<0.001). Moreover, hypertensive and diabetic individuals bearing A allele of IL-10 gene in high frequency were found to be more predisposed to stroke.     

Identification of SNP markers for common CNV regions and association analysis of risk of subarachnoid aneurysmal hemorrhage in Japanese population

Copy number variation (CNV) is emerging as a new tool for understanding human genomic variation, but its relationship with human disease is not yet fully understood. The data for a total of 317,503 genotypes were collected for a genome-wide association study of subarachnoid aneurismal hemorrhage (SAH) in a Japanese population (cases and controls, n = 497) using Illumina HumanHap300 BeadChip^®. To identify multi-allelic CNV markers, we visually inspected all genotype clusters of 317,503 SNP markers covering the whole genome using Illumina’s BeadStudio 3.0^® software. As a result, we identified 597 multi-allelic CNV markers for common (copy loss frequency > 0.05) CNV regions in a Japanese population (n = 497). The identified CNV markers shared the following characteristics: enrichment of Hardy–Weinberg disequilibria, Mendelian inconsistency among families, and high missing genotype rate. All annotated information for those markers is summarized in our database (http://www.snp-genetics.com/user/srch.htm). In addition, we performed case-control association analyses of identified multi-allelic CNV markers with the risk of subarachnoid aneurysmal hemorrhage. One SNP marker (rs1242541) within a CNV region neighboring the Sel-1 suppressor of lin-12-like protein (SEL1L) was significantly associated with a risk of SAH (P = 0.0006). We also validated the CNV around rs1242541 using real-time quantitative polymerase chain reaction (PCR). Information and methods used in this study would be helpful for accurate genotyping of SNPs on CNV regions, which could be used for association analysis of SNP markers within CNV regions.     

A1/A2 polymorphism of GpIIIa gene and a risk of aneurysmal subarachnoid haemorrhage

Platelet glycoproteins are involved in pathophysiology of cerebrovascular diseases. The aim of this study was to investigate the association between the GpIIIa gene A1/A2 polymorphism and a risk of aneurysmal subarachnoid haemorrhage (SAH) in a Polish population. In a case-control study we genotyped 288 Caucasian patients with aneurysmal SAH and 457 age-, gender- and race-matched controls. The GpIIIa A1/A2 polymorphism was genotyped with RFLP technique. No difference was found in the distribution of the polymorphism between the cases and controls (cases: A1A1—201 (69.8%), A1A2—83 (28.8%) and A2A2—4 (1.4%) vs. controls: A1A1—323 (70.7%); A1A2—128 (28.0%); A2A2—6 (1.3%), P > 0.05. In a multivariate analysis female gender (OR = 1.950; 95%CI: 1.308-2.907), hypertension (OR = 4.774; 95%CI: 3.048-7.478) and smoking (OR = 2.034; 95%CI: 1.366-3.030), but not GpIIIa A1/A2 polymorphism, were independent risk factors for aneurysmal SAH. The GpIIIa A1/A2 polymorphism is not a risk factor of aneurysmal SAH in a Polish population.     

Apolipoprotein E polymorphism in Saudis

Apolipoprotein E (apoE) genotypes were determined in 165 Saudis. The prevalence of genotype, E3/E3, E3/E4 and E4/E4 was found to be 71, 27 and 2% respectively. The E3/E3 was the most prevalent genotype among the Saudis followed by E3/E4. However, other genotypes E2/E2, E2/E3 and E2/E4 were absent showing the absence of E2 allele in the test population. The high frequencies of the E3 allele (0.845) and E3/E3 genotype (0.71) and absence of E2 allele in Saudis under study are similar to those reported earlier for Native Americans, Mexican-Americans, Mayans, Cayapa, Mazatecan Indians and Mexican Mestizos populations.     

Apolipoprotein E polymorphism in Saudis

Apolipoprotein E (apoE) genotypes were determined in 165 Saudis. The prevalence of genotype, E3/E3, E3/E4 and E4/E4 was found to be 71, 27 and 2% respectively. The E3/E3 was the most prevalent genotype among the Saudis followed by E3/E4. However, other genotypes E2/E2, E2/E3 and E2/E4 were absent showing the absence of E2 allele in the test population. The high frequencies of the E3 allele (0.845) and E3/E3 genotype (0.71) and absence of E2 allele in Saudis under study are similar to those reported earlier for Native Americans, Mexican-Americans, Mayans, Cayapa, Mazatecan Indians and Mexican Mestizos populations.     

Plasma visfatin,a possible prognostic marker in aneurysmal subarachnoid hemorrhage

Visfatin is linked to inflammation and associated with clinical outcomes of intracerebral hemorrhage. This study was designed to investigate whether visfatin might serve as a marker of severity and prognosis in aneurysmal subarachnoid hemorrhage. In this study, plasma visfatin levels of 172 consecutive patients and 172 sex and age-matched healthy subjects were determined using enzyme-linked immunosorbent assay. The recorded clinical outcomes included in-hospital mortality and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1–3). Plasma visfatin level was substantially higher in patients than in healthy controls (92.1 ± 20.5 ng/mL vs. 12.4 ± 3.2 ng/mL; P < 0.001), was significantly associated with the World Federation of Neurological Surgeons (WFNS) score (r = 0.569, P < 0.001) and Fisher score (r = 0.657, P < 0.001), was an independent predictor of in-hospital mortality [odds ratio (OR), 1.378; 95% confidence interval (CI), 1.036–1.866; P = 0.002] and 6-month mortality (OR, 1.261; 95% CI, 1.018–1.745; P = 0.004) and unfavorable outcome (OR, 1.207; 95% CI, 1.012–1.682; P = 0.008) in multivariate logistic regression analysis and had high predictive value for in-hospital mortality [area under curve (AUC), 0.849; 95% CI, 0.787–0.899; P < 0.001] and 6-month mortality (AUC, 0.868; 95% CI, 0.808–0.915; P < 0.001) and unfavorable outcome (AUC, 0.859; 95% CI, 0.797–0.907; P < 0.001) using receiver operating characteristic curves. AUCs of visfatin were similar to those of WFNS score and Fisher score (all P > 0.05), but visfatin did not improve the predictive values of WFNS score and Fisher score (all P > 0.05). Thus, visfatin may be associated with clinical severity of aneurysmal subarachnoid hemorrhage and also have prognostic value for clinical outcomes.     

Leptin as a marker for severity and prognosis of aneurysmal subarachnoid hemorrhage

Leptin has been identified as a plasma marker for outcomes in traumatic brain injury and intracerebral hemorrhage. We further investigated whether leptin might serve as a marker for severity and prognosis in aneurysmal subarachnoid hemorrhage. One hundred and eight consecutive patients and 108 sex and age – matched healthy subjects were recruited. Plasma leptin levels were measured by enzyme-linked immunosorbent assay. Clinical severity was assessed using World Federation of Neurological Surgeons score and Fisher score. Mortality and poor long-term outcome (Glasgow outcome scale scores of 1–3) at 6 months were recorded. Plasma leptin levels on admission were substantially higher in patients than in healthy controls, and were significantly associated with the clinical severity. There was also a significant association between leptin levels and clinical outcomes at 6 months in multivariate logistic regression analysis. Using receiver operating characteristic curves, we calculated areas under the curve for clinical outcomes at 6 months. The predictive performance of leptin was similar to, but did not obviously improve those of World Federation of Neurological Surgeons score and Fisher score. Thus, leptin may indicate clinical severity of the initial bleeding and also have prognostic value for clinical outcomes in aneurysmal subarachnoid hemorrhage and may therefore help in guiding treatment decisions in the setting of aneurysmal subarachnoid hemorrhage.     

Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations

ApoE phenotypes were determined in 615 unrelated Finnish individuals. The apoE gene frequencies observed (epsilon 2, 0.041; epsilon 3, 0.733; epsilon 4, 0.227) differ significantly from those in other populations. The frequency of the allele epsilon 2 was lower and that of epsilon 4 higher than in all other studied populations. Plasma lipids and apolipoproteins A-I, A-II and B were recorded in 207 of the typed subjects. By comparison with the most frequent homozygous apoE 3/3 phenotype, it was found that total cholesterol, LDL-cholesterol, and apoB concentrations were all markedly higher in apoE 4/4 and to a lesser degree in apoE 4/3 phenotypic groups. On the other hand, these lipid and apolipoprotein levels tended to be lower in E-2 heterozygotes. These data confirm and extend, in a different ethnic group, previous results of an effect of apoE genes on plasma lipoprotein concentrations. The data suggest that the apoE gene locus may be one factor responsible for the high LDL cholesterol concentrations in the Finnish population.     

Inverted Y chromosome polymorphism in the Gujerati Muslim Indian population of South Africa

Summary An inverted Y chromosome has been found at a very high frequency in a Muslim Indian community living in the Johannesburg-Witwatersrand area of the Transvaal Province of South Africa: 8 of 141 (5.7%) retrospectively identified Indian males had an inv(Y)(p11.2q11.23) and all were of the Muslim faith. The inversion was found in 22 of 72 (30.5%) prospectively studied normal Muslim Indian males. All the carriers of the inversion were Gujarati-speakers whose families migrated to the Transvaal from the Gujerat Province of India during the first half of this century. The origins of the ancestors of the individuals with inv(Y) were traced to a small village, Kholvad, near the city of Surat, and some neighbouring villages. The polymorphic frequency of the inv(Y) has probably been produced through random genetic drift in a reproductively isolated community, maintained by strict endogamous marriage customs based on religious and linguistic affiliations. There was no indication that the inverted Y was associated with any reproductive disadvantages.     

动脉瘤性蛛网膜下腔出血后早期脑损伤的研究现状

蛛网膜下腔出血(subarachnoid hemorrhage,SAH)是临床上最具破坏性和难以治疗的神经疾病之一,尤其是动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)。尽管经过数十年的研究,我们对aSAH病理生理学的认识和动脉瘤破裂的处理(包括手术夹闭或血管内治疗)有所改善,但a SAH仍然是中国和世界范围内严重和显著的健康问题。aSAH后造成脑损伤的机制至今仍不清楚。传统上,在动脉瘤破裂后3～7天内出现的脑动脉痉挛被认为是脑损伤的最重要决定因素,所以大多数的体内研究都着重强调了迟发性脑血管痉挛在aSAH后的病理生理学或形态学上变化的基本机制。然而,最近的研究表明,预防迟发性脑血管痉挛的发生并不能改善患者的预后。这一发现最终将重点转向了早期脑损伤对aSAH患者预后的影响上。大量的证据表明,脑损伤从动脉瘤破裂开始,随着时间的推移而发生变化,在患者的预后中起着重要的作用。因此,文章将从a SAH后脑损伤机制开始,回顾aSAH的研究历史,以及早期脑损伤的当前研究现状和未来发展。     

Apolipoprotein E polymorphism in normal Han Chinese population: frequency and effect on lipid parameters

Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence and effect on lipid parameters in normal Han Chinese population. Fragments of ApoE gene forth exon containing codon 112 and 158 polymorphic locus were amplified by PCR, and then digested with Cfo I endonuclease. Genotypes and alleles frequencies of 168 healthy Han Chinese were calculated. The frequency of genotypes ε3/3, ε3/4, and ε2/3 was found to be 75.00, 10.70, and 11.90%, respectively, and 0.60, 1.20, and 0.60% for ε2/2, ε2/4, and ε4/4. The effects of ApoE genotypes and alleles on lipid parameters were analyzed. The effects of ApoE alleles on TC, LDL-C, ApoB was: along a decreasing gradient ε4 > ε3 > ε2. The effect of ε4 allele was to increase serum levels of TC, LDL-C and ApoB, and ε2 allele had an effect opposite to that of ε4 allele. Results obtained in this study indicate that ApoE polymorphism is an independent genetic factor on individual serum levels of lipids and apolipoproteins. Shu Liang and Min Pan should both be considered first authors.     

Apolipoprotein B 3'-VNTR polymorphism in the Udmurt population

An analysis of a highly polymorphic region of the apolipoprotein B gene 3'-end DNA (Apo B 3'-VNTR), represented by 10 alleles, was carried out using the polymerase chain reaction. Data inferred from the principal component analysis indicate that the Udmurts occupy an isolated position among the populations constituting the northern branch of Caucasoid peoples.     

Increased levels of F2-isoprostanes following aneurysmal subarachnoid hemorrhage in humans

Subarachnoid hemorrhage (SAH) resulting from aneurysmal rupture is the major cause of nontraumatic SAH. We hypothesized that oxidative stress could be increased following aneurysmal SAH due to hemoglobin release and ischemia-reperfusion injury and that may further contribute to poor outcome. We collected plasma and cerebrospinal fluid (CSF) samples from 11 non-SAH controls and 15 aneurysmal SAH patients for up to 10 days after surgery and investigated status of oxidative stress in patients. Results showed that mean or peak levels of F(2)-isoprostanes (F(2)-IsoPs), a specific marker of lipid peroxidation, and total nitrate/nitrite, metabolites of nitric oxide and peroxynitrite, in CSF and plasma were significantly higher in SAH patients than in controls. First-day levels were also higher in CSF, but not in plasma, in SAH patients. Moreover, mean and peak levels of CSF F(2)-IsoPs were positively correlated with poor outcome or severity of clinical conditions in patients. Furthermore, levels of retinol, delta-tocopherol, beta+gamma-tocopherol, lutein, beta-carotene, and coenzyme Q(10) in plasma were significantly lower in SAH patients than in controls. Our results indicate that oxidative damage may play important roles in the severity and complications of aneurysmal SAH and suggest that means to suppress lipid peroxidation may be beneficial in improving the outcome of aneurysmal SAH.     

Effect of NBS1 gene polymorphism on the risk of cervix carcinoma in a northern Indian population

Cervical cancer is one of the most common neoplastic diseases affecting women, with a worldwide incidence of almost half a million cases. A history of smoking and use of oral contraceptives have been confirmed to be risk factors for cervical cancer. Genetic susceptibility and immune response, especially impaired cellular immune response, may well be related to the development of cervical cancer. NBS1 is one of the key proteins participating in the recognition and repair of double-strand breaks that may lead to genomic instability and cancer if unrepaired. The objective of the present study was therefore to investigate NBS1 Glu185Gln gene polymorphisms and the risk of cervix cancer in a northern Indian population. We found that passive smokers having particular NBS1 genotypes (Glu/Gln, Gln/Gln or Glu/Gln + Gln/Gln)have an increased risk of developing cervix cancer (OR 5.21, p=0.000001; OR 4.60, p=0.001; OR 5.10, p=0.0000009, respectively).The risk was increased 2.4-fold in oral contraceptive users with a Glu/Gln genotype. We conclude that the risk of cervical cancer is increased in passive smokers and in users of oral contraceptives with certain NBS1 genotypes.     

Apolipoprotein E polymorphism in elderly Japanese-Brazilian immigrants does not explain the reduced cardiovascular risk factor incidence

Study of immigrant populations may contribute to a better understanding of the epidemiology of diseases associated with the aging process. We examined the prevalence of cardiovascular risk factors, including apolipoprotein E (ApoE) polymorphism, in elderly subjects who were born in Japan, migrated to South Brazil and have lived in that region for over 40 years, versus a group of elderly, locally born Brazilians living in the same region. These Japanese subjects came to Brazil after World War II (1950-1960) from several Japanese cities, mainly Nagasaki, Kumamoto and Hokkaido. Among 1007 subjects genotyped for ApoE polymorphism, we selected 540 elderly subjects (>60 years old), consisting of 270 Japanese-Brazilians and 270 Brazilians of European ancestry from Rio Grande do Sul State (Gaucha population). The Japanese-Brazilian group had significantly lower prevalences of obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome than did the Gaucho population group. ApoE polymorphism frequencies were similar in the two groups. The differences in cardiovascular risk factors observed in the two populations cannot be explained by ApoE polymorphism; they could be related to conservation of Japanese lifestyle habits, such as diet.     

The inverted Y-chromosome polymorphism in the Gujarati Muslim Indian population of South Africa has a single origin.

Y-specific polymorphisms were studied in Gujarati Muslim Indians possessing a Y-chromosome pericentric inversion [inv(Y)] in an attempt to prove a common genetic origin for the inversion. The p49a/TaqI and p49a/PvuII haplotypes were determined for 9 normal and 8 inv(Y) Gujarati Muslim men. Men with the inversion possessed identical TaqI and PvuII profiles, as opposed to 7 different TaqI and 8 different PvuII haplotypes observed in the 9 normal men. These results provide conclusive evidence for a common genetic origin of the inverted Y chromosome observed in this Gujarati Muslim community.     

Apolipoprotein E genotyping among the healthy Kuwaiti population

Apolipoproteins (lipid-free) are lipid-binding proteins that circulate in the plasma of human blood and are responsible for the clearance of lipoproteins. Apolipoprotein E (ApoE) is one of the several classes of this protein family. It acts as a ligand for the low-density lipid (LDL) receptors and is important for the clearance of very low-density lipid (VLDL) and chylomicron remnants. The APOE gene locus is polymorphic, with three major known alleles, APOE*3, *4, and *2. We investigated the distribution of the allele frequency of the APOE gene locus and describe here the genetic variation in four Kuwaiti subpopulations: Arab origin (Arabian peninsula), Arab Bedouin tribes, Iranian origin, and the heterogeneous population. We also describe the use of Spreadex gels in resolving the amplified and digested products of the APOE gene locus. DNA was extracted from whole blood and subjected to PCR and then to RFLP analysis. Allele and genotype frequencies were estimated for the total population and for each subpopulation. Statistical analysis showed no difference in the allele frequencies between the four groups. The frequency of APOE*3 in the Kuwaiti population was highest (88.4%) followed by the frequency of APOE*4 (6.5%) and APOE*2 (5.1%). The genotype and allele frequencies obtained for the Kuwaiti population fell within the reported worldwide distribution for the APOE gene locus. Moreover, the results obtained in this study showed no statistical difference (p > 0.05) between the APOE allele and genotype frequencies between the subgroups for all six genotypes and three alleles, supporting the assumption of admixture in the Kuwaiti population and that the obtained frequencies were in Hardy-Weinberg equilibrium. Finally, we found that the distribution of the APOE alleles in Kuwait differs somewhat from those reported in other Arab populations, suggesting that the Arabs originating from the Arabian peninsula are different from those of Lebanon, Morocco, and Sudan.     

Endothelial nitric oxide synthase gene polymorphisms and the risk of acute myocardial infarction in a South Indian population

Myocardial infarction (MI) is a complex multi-factorial, polygenic disorder which results from an interaction between a person’s genetic makeup and various environmental factors. Nitric oxide (NO), a potent vasodilator produced by endothelial cells, plays an important role in the regulation of blood pressure, regional blood flow and also inhibits platelet aggregation, vascular smooth muscle cell proliferation and leukocyte adhesion to vascular endothelium. Our aim was to analyze the association of NOS3 (endothelial nitric oxide synthase 3) 894G>T and ?786T>C gene polymorphisms and MI risk in the South Indian population. A total of 287 MI patients, 279 risk control patients and 321 healthy controls were recruited for the retrospective study. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was no significant association observed between NOS3 894G>T, ?786T>C polymorphisms and MI. A significant difference was observed in the distribution of GT genotype of the NOS3 894G>T polymorphism between the cases and the risk controls (p = 0.05) but the odds ratio (0.6) did not show risk for MI. The present study showed lack of association between NOS3 gene polymorphisms and MI in South Indian population.