Study of the association between constitutional exogenous obesity and polymorphism of the apolipoprotein B gene

An attempt was made to associate the insertion-deletion (Ins/Del) polymorphism of the apolipoprotein B gene (apoB) with obesity and to identify alleles and genotypes predisposing to this disorder. The apoB Ins/Del allele frequencies observed in the Russian population were similar to those in West European populations and significantly differed from frequencies reported for Asian populations. Patients with obesity did not differ from healthy individuals in allele and genotype frequencies regardless of whether total or sex-stratified samples were compared. Estimation of relative risk for individuals with genotype Ins/Ins did not reveal a significant association between obesity and this genotype. Thus, constitutional exogenous obesity did not prove to be associated with the Ins/Del polymorphism of the apoB gene in the Russian population.     

Apolipoprotein B signal peptide polymorphism: distribution and influence on lipid parameters in Tunisian population

Apolipoprotein B (apo B) is the major protein component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, the insertion/deletion polymorphism located in the coding part of the signal peptide of apo B, associated with modification of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. No such study in the Tunisian population has been performed. The aim of our study was to assess the effect of insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in a sample of the Tunisian population. A total of 458 unrelated subjects (321 men and 137 women) were included. The insertion/deletion polymorphism was determined by electrophoresis on polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.74 and 0.26, respectively. These frequencies were similar to those found in other Caucasian populations. There was no significant difference in serum TC, TG, and HDL-C levels due to the influence of the genotypes. However, significant variation among the three genotypes was seen for LDL-cholesterol (p<0.001) and apo B (p<0.001) levels. Individuals homozygous for the Del allele had higher levels than individuals homozygous for the Ins allele, while individuals heterozygous for both alleles exhibited intermediate levels. When the data were analyzed in men and women separately, a similar effect was seen in both groups. Our results show that distribution of apo B insertion/deletion polymorphism in Tunisians is similar to other Caucasian population and confirm the reported association with serum LDL-cholesterol and apo B concentrations.     

Dopamine D2 receptor gene −141C Insertion/Deletion polymorphism in Turkish schizophrenic patients

Schizophrenia is a chronic and neuropsychiatric disease that affects about 0.5–1% of the world’s population. An increase in dopamine and dopamine D2 receptor (DRD2) gene products has been well described in schizophrenic patients. Several groups have studied the relationship between dopaminergic hyperactivity and cellular communications have obtained discordant results. Studies searching for the relationship between the schizophrenia and DRD2 gene have gained more interest. Our objective was to determine the relationships among schizophrenic symptoms in schizophrenia subtypes and severity of symptoms in terms of DRD2 gene −141C Insertion/Deletion [Ins/Del; I/D] polymorphism by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) assay method. Genomic DNA was prepared from peripheral blood by using salt extraction method. After amplification of genomic DNA, PCR products were digested with BstNI restriction enzyme for the detection of DRD2 gene −141C Ins/Del polymorphism in 73 schizophrenic patients and 60 healthy control subjects. The allelic frequencies of the DRD2 gene −141C Ins/Del polymorphism in case and control groups were 79.5 and 77.5% for I allele; 20.5 and 22.5% for D allele respectively. There was no significant difference in frequencies of genotypes and alleles between the two groups. In schizophrenic and control subjects, there were no significant relationship in severity of the disease and schizophrenia types among the −141C Ins/Del genotypes and alleles.     

中国汉族apoB基因EcoRI、XbaI、MspI、Ins/Del及3＇端VNTR位点的多态性研究

目的：apo B基因多态性对群体遗传学、心血管疾病等研究领域有着重要的价值,本文分析了中国汉族人群中apoB基因EcoRI、XbaI、MspI、Ins/Del及3＇端VNTR等5个多态性位点的等位基因频率分布,为相关研究提供基础资料。方法：应用PCR-RFLP技术分析EcoRI、XbaI、MspI等3个位点的多态性分布,应用常规PCR方法分析Ins/Del及3＇端VNTR等2个位点的多态性分布。结果：1人群中EcoRI位点有E＋及E-两种等位基因,基因频率分别为87.1%和12.9%;XbaI位点有X＋及X-两种等位基因,基因频率分别为6.1%和93.9%;MspI位点有M＋及M-两种等位基因,基因频率分别为97.1%和2.3%;Ins/Del位点有Ins及Del两种等位基因,基因频率分别为70.7%和29.3%;3＇端VNTR位点有16种等位基因,其中以HVE34与HVE36最为常见,频率分别为33.4%与21%。2连锁不平衡分析表明,5个位点间除XbaI与Ins/Del间存在较弱的连锁不平衡（D＇=0.911,r2=0.175）,其余点位间无显著连锁不平衡。结论：数据比对表明,5个多态性位点的基因型和等位基因频率存在民族、种族差异,因此在apo B基因相关研究中应充分考虑遗传背景造成的影响。     

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.     

Analysis of the Genetic Structure of the Breeding Nucleus of the Russian Population of Thoroughbred Horses by the ExtensionLocus Molecular DNA Typing

Results of the first in Russia survey of the gene pool of the breeding nucleus of the Russian population of thoroughbred horses by means of PCR analysis of the E(Extension) locusMC1Rgene mutations are presented. The data on the structure of breeding populations from the leading stud farms Voskhod and Oros with regard to color phenotypes as well as genotype and allele frequencies are presented. The population structure parameters are discussed with respect to possible specific features of microevolution processes.     

ACE and LRPAP1 insertion-deletion polymorphisms in a northern Ivory Coast population

The ACE and the LRPAP1 gene insertion-deletion polymorphisms were determined in 133 healthy individuals sampled from Ouangolodougou, a village located in northern Ivory Coast. No sex differences were found in ACE and LRPAP1 gene frequencies. The ACE insertion and deletion alleles had frequencies of 0.346 and 0.654, respectively. The ACE gene was not in Hardy-Weinberg equilibrium because of an excess of heterozygote genotypes and a deficiency of I/I genotypes compared to the expected values. Statistical analysis showed a significantly lower frequency of I/I genotypes in the Ivory Coast population compared to Sudan, Kenya, African Americans, and African Brazilians (p < 0.05), whereas no differences were found with respect to Somalia. Conversely, the frequencies of the insertion and deletion alleles in the Ivorian population did not differ from those of other African populations. The LRPAP1 insertion and deletion allele frequencies found in our study (0.192 and 0.808, respectively) did not differ significantly from the Czech and Spanish populations, the only two populations previously characterized for this polymorphism. However, the frequency of the I/I genotype was significantly lower than the frequencies observed in the European samples. Because of the limited information on the LRPAP1 gene polymorphism distribution in worldwide populations, it was not possible to draw any conclusion.     

A meta-analysis of association of vitamin D receptor BsmI gene polymorphism with the risk of type 1 diabetes mellitus

Abstract

Association between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism and the risk of type 1 diabetes mellitus (T1DM) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI gene polymorphism and the risk of T1DM using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Twenty-three reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with T1DM susceptibility. In overall populations, bb genotype was associated with T1DM, but the B allele and BB genotype were not. In Asians and Latino population, B allele and bb genotype were associated with TIDM risk, but BB genotype was not. In Caucasians, VDR BsmI gene polymorphism was not associated with the T1DM risk. In Africans, B allele and BB genotype were associated with T1DM risk, but the bb genotype was not. However, the sample size for Latino population and Africans was small. In conclusion, VDR BsmI B allele, bb genotype was associated with T1DM risk in Asians, and bb genotype was associated with T1DM risk in overall populations. However, more studies should be conducted to confirm it.     

Analysis of clusterin gene (CLU/APOJ) polymorphism in Alzheimer’s disease patients and in normal cohorts from Russian populations

Mutations in three genes PSEN1, PSEN2, and APP are known to be a cause of familial forms of Alzheimer’s disease (AD). APOE gene polymorphism is a strong risk genetic factor for AD. We have evaluated allele and genotype frequency distribution of rs11136000 polymorphism in the clusterin (CLU) gene (or apolipoprotein J, APOJ) in the samples from three Russian populations and in AD patients. Genome-wide association studies in samples from several European populations have recently revealed the highly significant association of CLU gene with AD (p = 8.5 × 10^?10). We found no differences in allele and genotype frequencies of rs11136000 between the populations from the Moscow, Ural, and Siberia regions. The allele frequencies are close to those in European populations. The genetic association analysis in cohort of AD patients and normal individuals (>500 individuals in each group) revealed no significant association of the rs11136000 polymorphism in CLU gene with Alzheimer’s disease in Russian populations. Although our results showed that the CLU gene polymorphism rs11136000 is likely not a major genetic factor for the common form of Alzheimer’s disease, the data do not rule out the possibility of a modest effect of CLU and interaction between CLU and APOE genotypes in etiology of Alzheimer’s disease.     

Population genetic analysis of 15 autosomal STR loci in the Russian population of northeastern Inner-Mongolia, China

In the present study, we investigated the genetic polymorphisms of 15 autosomal STR loci in the Russian population of northeastern Inner-Mongolia, China as well as its genetic relationships with other populations. DNA typing for 15 autosomal STR loci was performed on 148 randomly selected healthy individuals from the Russian population living in Eerguna, northeastern Inner-Mongolia. Allelic frequencies of these loci were calculated by direct counting. The genotype data of this Russian population was moreover compared to other populations using neighbor-joining method, as such constructing a phylogenic tree. A total of 143 alleles were found in the Russian population with corresponding allele frequencies in the range from 0.0034 to 0.5372. Among all the 15 loci, D18S51 had the highest polymorphism (PIC = 0.8632), whereas TPOX had the lowest (PIC = 0.5179). In the phylogenic tree, this Russian population has a close relationship with the populations of South Siberia and northeastern Asia. This study may increase our understanding of the genetic background of the Russian population in Eerguna, China as such providing useful information for anthropological research, forensic sciences as well as disease-association studies.     

Effects of intragenic variability at 3 polymorphic sites of the apolipoprotein B gene on serum lipids and lipoproteins in a multiethnic Asian population.

We determined the allelic (X+/X-, M+/M-, and E+/E-) distribution frequencies of the XbaI, MspI, and EcoRI restriction fragment length polymorphisms (RFLPs) in the apolipoprotein B gene in a control group of 374 healthy Chinese, Malays, and Indians and in a hyperlipidemic cohort of 131 Chinese patients. Covariability between the RFLPs and serum lipid, lipoprotein, and apolipoprotein concentrations was also studied. We found a lower frequency (average 0.0829) of the X+ allele and higher frequencies of the E+ (average 0.9452) and M+ (average 0.9772) alleles in our study population compared with frequencies reported in other populations. The 3 polymorphic sites did not contribute to significant variations in lipid levels (p > 0.1 in all cases). Also, there was no significant variation in genotype frequencies between the control subjects and the hyperlipidemic subjects. Despite their relative close proximity within the APOB gene sequence, the 3 polymorphic sites did not show any significant linkage disequilibrium. However, the presence of the X+ cutting site was in linkage disequilibrium with the Del allele of the 5' insertion-deletion polymorphism and the E-allele was in linkage disequilibrium with the 3' VNTR located near the 3' end of the coding region of the APOB gene.     

Association of a polymorphism of ABCB1 with obesity in Japanese individuals

The aim of the present study was to identify gene polymorphisms that confer susceptibility to obesity. A total of 5448 unrelated Japanese individuals from two independent populations were examined: subject panel A comprised 4252 individuals who visited participating hospitals; subject panel B comprised 1196 community-dwelling elderly individuals. The genotypes for 95 polymorphisms of 67 candidate genes were determined. The χ² test revealed that six polymorphisms were related (p < 0.05) to the prevalence of obesity in subject panel A; after application of Bonferroni's correction, however, only the 2677G → A/T polymorphism (rs2032582) of the ATP-binding cassette, subfamily B, member 1 gene (ABCB1) was significantly associated (p = 0.0003) with obesity. Subsequent multivariable logistic regression analysis also revealed that the 2677G → A/T polymorphism of ABCB1 was significantly associated with obesity. For validation of this association, the 2677G → A/T polymorphism of ABCB1 was examined in subject panel B and again found to be significantly associated with obesity. Body mass index was significantly (p = 0.01) greater for individuals with the variant T allele of this polymorphism than for those with the GG genotype in the combined subject panels A and B. Our results suggest that the ABCB1 genotype may prove informative for assessment of genetic risk for obesity in Japanese individuals.     

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in Tunisian population

Abstract

Context: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting.

Objective: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians.

Materials and methods: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III.

Discussion: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III.

Conclusion: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.     

Association of GNB3 gene C825T polymorphism with coronary heart disease

The C825T polymorphism in the gene encoding the G protein beta 3 subunit (GNB3) causes enhanced G protein activation and the increased in vitro cell proliferation. We investigated the association of gene GNB3 C825T polymorphism with coronary artery disease (CAD) in the Russian population. A total of 313 patients with CAD diagnosed on the basis of clinical studies and coronary angyography were examined. The control group included 132 individuals that lacked clinical CAD symptoms and had matching profile of coronary artery disease risk factors. Blood pressure was measured using standard protocols. Increased levels of diastolic and systolic pressure was observed in both groups. The allele and genotype frequencies of this polimorphic marker were significantly higher in the CAD patients than in control. We found that the frequency of allele C and gen-. otype CC was significantly higher in the CAD patients (OR = 1.55; P = 0.0079; OR = 1.63; P = 0.0215, respectively), which suggests higher risk of this pathology in carriers of allele C and genotype CC. Thus, in the Russian population coronary artery disease is associated with GNB3 allele C and genotype CC.     

Dynamics of a Lactate Dehydrogenase Polymorphism in the Wood Louse PORCELLIO SCABER Latr.: Evidence for Partial Assortative Mating and Heterosis in Natural Populations

Electrophoretic separation of lactate dehydrogenase (LDH) of Porcellio scaber from 14 natural populations in California, and one each in Oregon, Delaware and Massachusetts, indicates a biallelic polymorphism. Phenotypes are recovered from laboratory matings of virgin females in frequencies agreeing with simple Mendelian inheritance, and the frequency distributions of phenotypes in natural populations are typically in agreement with the appropriate Hardy-Weinberg distributions for these same populations. The same allele predominates in all natural populations examined. Temporal stability within populations suggests that the polymorphism is at, or near, equilibrium. The spatial distribution of allele frequencies, however, is apparently mosaic. Abrupt discontinuities in gene frequency over short distances (50 m to 1 km) suggest that interpopulation migration is insufficient to swamp local differences in gene frequency. Analysis of the transmission dynamics of the polymorphism in natural populations using mother-offspring genotype comparisons suggests that the allelic frequencies of transmitted male gametes are not independent of female genotype. Specifically, the observed mating scheme in natural populations appears to be partially assortative. Comparisons of progeny genotype distributions with yearling (or adult) genotype distributions from the same populations indicate a superior post-partum viability of heterozygous individuals relative to homozygotes. The distortion of progeny genotypic distributions created by assortment is thus apparently counteracted by subsequent heterosis.     

Gene polymorphism of the renin-angiotensin system in six ethnic/geographic regions of Belarus

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and the T174M polymorphism of the angiotensinogen gene (AGT) have been studied in six ethnic/geographic regions of Belarus. Significant intrapopulation differences in ACE genotype frequencies have been found for the northern and eastern regions (the Dvina and Dnepr basins, respectively). Significant differences in the AGT genotype frequencies have been found between populations of the Dnepr basin and populations of all other Belarusian regions. The allele and genotype frequencies of the genes studied in the Belarusian population and populations of other regions of the world have been compared. The frequencies of the insertion (I) and deletion (D) alleles of the ACE gene in the Belarusian population are 50.7 and 49.3%, respectively, which is similar to these frequencies in European countries. The frequency of the M allele of the AGT gene in Belarus is 16.6%, which is higher than its frequency in populations of European, African, and Asian origins.     

Gene polymorphism of the renin-angiotensin system in six ethnogeographic regions of Belarus

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene (ACE) and the T174M polymorphism of the angiotensinogen gene (AGT) have been studied in six ethnogeographic regions of Belarus. Significant intrapopulation differences in ACE genotype frequencies have been found for the northern and eastern regions (the Dvina and Dnepr basins, respectively). Significant differences in the AGT genotype frequencies have been found between populations of the Dnepr basin and populations of all other Belarusian regions. The allele and genotype frequencies of the genes studied in the Belarusian population and populations of other regions of the world have been compared. The frequencies of the insertion (I) and deletion (D) alleles of the ACE gene in the Belarusian population are 50.7 and 49.3%, respectively, which is similar to these frequencies in European countries. The frequency of the M allele of the AGT gene in Belarus is 16.6%, which is higher than its frequency in populations of European, African, and Asian origins.     

The HHEX rs1111875A/G gene polymorphism is associated with susceptibility to type 2 diabetes in the iranian population

The illuminating picture of genetic mechanisms underlying the development of type 2 diabetes (T2DM) includes differently accumulated genetic polymorphisms that increase the risk along with environmental factors. A number of single nucleotide polymorphisms (SNPs) are indicated to be linked with T2DM, but also conflicting results have been found. To examine the contribution of these polymorphisms in conferring susceptibility to T2DM, the association of HHEX rs1111875A/G and CDKN2A/B rs10811661C/T common gene polymorphisms with the risk of T2DM in an Iranian population was evaluated. In this study participated 140 patients and 140 controls. Genomic DNA was extracted from samples and genotyping of the polymorphisms was performed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. A significant association was found with the G allele (OR = 1.729, CI = 1.184–2.523, P = 0.004) and GG genotype (OR = 2.921, 95% CI = 1.789–4.771, P< 0.001) of the rs1111875A/G SNP for susceptibility to T2DM in the recessive model. Furthermore, compared with the GG genotype, individuals with the GA genotype had a lower risk to develop T2DM (OR = 0.237, 95% CI = 0.137–0.408, P< 0.001) in the additive model. In addition, an association between the polymorphism and BMI in regard to the risk of T2DM was identified. The genotype and allele frequencies of the rs10811661C/T polymorphism did not show a statistically significant association with T2DM in any genetic model. Our results show that the rs1111875A/G polymorphism is an important susceptibility polymorphism for the development of T2DM in the Iranian population. Also, these findings support that this polymorphism is a key genetic risk factor for the development of T2DM in multiple ethnic populations.

     

Genotype and allele frequency of human multidrug resistance (MDR1) gene C3435T polymorphism in Denizli province of Turkey

Human p-glycoprotein encoded by human multidrug resistance (MDR1) gene, is a transmembrane protein that serves as efflux pump for a wide variety of lipophilic compounds possessing a physiological role in protecting cells against the DNA damaging of certain xenobiotics. According to the published data, the frequency of C3435T polymorphism differs depending on the different ethnical populations such as Asian, African, and Caucasians populations. In our study, we identified the MDR1 C3435T polymorphism in 150 healthy volunteers in Denizli province of Turkey. DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction–restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. We obtained CC, CT and TT genotype frequencies as 20, 53 and 27%, respectively. According to our results, the C allele in Turkish population (Denizli province, west of Turkey) is found 47% and this data shows similarity with Caucasian (UK and German) populations and significantly lower than African populations (p < 0.001). Our study is the first data on the genotype and allele frequency of the human multidrug resistance (MDR1) Gene C3435T Polymorphism in Denizli Province at regional basis in Turkey. Our results could serve as a basis for large-scale correlation studies on the relevance of C3435T genotype in cancer therapy and other diseases in Turkish population. Investigation of genotype frequencies related with p-glycoprotein substrates should be investigated in large scale at regional bases in Turkish population. The scaled-up data might help either to the use of p-glycoprotein substrates to be used for therapeutic applications and population genetics considering the genotype frequencies possibly occurring throughout the history in Anatolian basin.     

Susceptibility to chronic thromboembolic pulmonary hypertension may be conferred by miR-759 via its targeted interaction with polymorphic fibrinogen alpha gene

A deletion/insertion (Del/Ins) polymorphism of 28 base pairs (bp) in the 3′ untranslated region (UTR) of fibrinogen alpha gene (FGA) was associated with thromboembolic diseases, but the underlying mechanisms remain unknown. Computational predication reveals that the 28 bp polymorphic fragment is complementary to the sequence of a microRNA, miR-759. In this study, we aim to investigate the association and implicated mechanisms between FGA polymorphisms and the susceptibility to chronic thromboembolic pulmonary hypertension (CTEPH). The Del/Ins polymorphism was analyzed in 190 patients with CTEPH and 628 controls. The FGA 3′UTR and miR-759 interaction was investigated using luciferase assay and quantitative RT-PCR method. Expression of miR-759 and FGA in human tissues was investigated by RT-PCR. The results reveal that the allele frequency of Ins was significantly higher in the patients than in the controls (55.8 vs. 47.1%, P = 0.003, odds ratio = 1.42, 95% confidence interval: 1.13–1.79). Both miR-759 and FGA were expressed in human liver. Co-transfection of miR-759 decreased the expression and mRNA stability of reporter gene containing the FGA 3′UTR. The effect of miR-759 was stronger on the Ins allele than on the Del allele. These observations suggest that the expression of FGA was regulated by miR-759 through its interaction at the polymorphic 3′UTR sequence, which was associated with the susceptibility to CTEPH.