The interleukin-1 receptor antagonist gene and the inhibitor of kappa B-like protein gene polymorphisms are not associated with myocardial infarction in Slovene population with type 2 diabetes

In this study we investigated the association of the interleukin-1 receptor antagonist gene variable number tandem repeat (IL1RN VNTR) polymorphism and of the inhibitor of kappa B-like protein (IKBL) gene polymorphism with myocardial infarction (MI) in a group of patients with type 2 diabetes. The IL1RN VNTR and the IKBL+ 738T > C gene polymorphisms were tested in 374 Caucasians: 151 cases with MI and 223 subjects with no history of coronary artery disease. The IL1RN VNTR polymorphism was not a risk factor for MI in Caucasians with type 2 diabetes (genotype 22 vs. the rest: odds ratio (OR) 1.6; 95% confidence interval (CI) = 0.8-3.5; p = 0.2). We also failed to demonstrate that IKBL+ 738T > C gene polymorphism was associated with MI in patients with type 2 diabetes (OR = 0.9; 95% CI = 0.3-2.6; p = 0.9). We provide evidence that the IL1RN VNTR and the IKBL + 738T > C gene polymorphisms are not risk factors for MI in Caucasians with type 2 diabetes.     

SP110 polymorphisms are not associated with pulmonary tuberculosis in a South African population

Susceptibility to tuberculosis (TB) in mice has recently been attributed to the Ipr1 gene. Polymorphisms in the human homologue, SP110, have been investigated in various populations with only one study finding an association with TB susceptibility. We investigated eight SP110 polymorphisms in a South African population, including two novel polymorphisms. No significant association was found with any of the polymorphisms investigated, including two polymorphisms that were previously found to be associated with TB susceptibility in West African populations.     

GRM7 polymorphisms are not associated with ischemic stroke in Iranian population

Abstract

Objectives: Ischemic stroke is the main neurological cause of acquired incapability in adults and a prominent cause of mortality. Several association studies have been conducted to explore the role of candidate genes in this neurological condition.

Methods: In the present study, we aimed at identification of association between Glutamate Metabotropic Receptor 7 (GRM7) and risk of ischemic stroke in Iranian population. Two intronic variants within this gene (rs6782011 and rs779867) were genotyped in 318 sporadic ischemic stroke cases and 300 unrelated, healthy controls individuals.

Results: No significant difference was found in allele, genotype or haplotype frequencies of these SNPs between cases and controls after correction for multiple comparisons.

Conclusion: Consequently, the assessed GRM7 variants are not implicated in risk of ischemic stroke in Iranian population.     

Single nucleotide polymorphisms in the mitochondrial control region are associated with metabolic phenotypes and oxidative stress

Objective

To identify the mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in the control region and elucidate their role in metabolic phenotypes and oxidative stress.

Methods

A total of 861 nondiabetic subjects were enrolled, including 250 impaired fasting glucose (IFG) and 370 obese subjects (body mass index [BMI] > 25 kg/m²). Antioxidant status presented as total free thiol level was determined from serum samples. DNA was extracted from peripheral blood leucocytes, and the sequences were analyzed using the DNASTAR software. SNPs were identified by comparison with the Cambridge Reference Sequence.

Results

After adjusting odds ratios for age, sex, and BMI, the selected independently significant SNPs indicated 4 susceptible SNPs: SNP-16126C and SNP-16261T, which were related to abdominal obesity (P = 0.009; 0.06); SNP-16390A, related to hypertension (HTN) (P = 0.007); and SNP-16092C, related to decreased antioxidant capacity (P = 0.015). In the obese subgroup, 3 susceptible SNPs included SNP-16189C and SNP-16260T, which showed significantly higher IFG prevalence (P = 0.016 and 0.024, respectively), and SNP-16519C, which was significantly higher in the HTN group (P = 0.036). As to protective SNPs, 5 protective SNPs were identified in all subjects but only one SNP-16093C is consistent in obese group, which showed a significantly lower prevalence in patients with abdominal obesity and was associated with a higher antioxidant status (P < 0.001).

Conclusion

SNPs in the mtDNA control region are associated with metabolic phenotypes and oxidative stress markers. Some SNPs are relating to the interaction between obesity and genetic factors. The beneficial effects of these protective SNPs were insignificant and some susceptible SNPs became dominant within the obese subgroup. Subjects harboring these SNPs should avoid excessive weight gain.     

Single nucleotide polymorphisms of the MCHR1 gene do not affect metabolism in humans

Melanin concentrating hormone receptor-1 (MCHR1) is a centrally and peripherally expressed receptor that regulates energy expenditure and appetite. Single nucleotide polymorphisms (SNPs) of the MCHR1 gene have been previously associated with obesity, but the results are inconsistent among different populations. This study was performed to determine whether SNPs of MCHR1 affect glucose and energy metabolism. We screened six SNPs of MCHR1 in a cross-sectional study of 217 middle-age, non-diabetic Finnish subjects who were offspring of type 2 diabetic patients. Insulin secretion was evaluated by an intravenous glucose tolerance test and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry. SNPs of MCHR1 were not associated with BMI, waist circumference, subcutaneous or intra-abdominal fat area, glucose tolerance, first-phase insulin release, insulin sensitivity, or energy metabolism. One SNP, which was in >0.50 linkage disequilibrium with the other five SNPs, was also screened in 1455 unrelated Finnish middle-age subjects in a population-based study. No differences in BMI, waist circumference, or glucose or insulin levels in an oral glucose tolerance test among the genotypes were found. In conclusion, SNPs of MCHR1 did not have effects on metabolic variables in humans.     

Genetic polymorphisms of the TYMS gene are not associated with congenital cardiac septal defects in a Han Chinese population

Background

Clinical research indicates that periconceptional administration of folic acid can reduce the occurrence of congenital cardiac septal defects (CCSDs). The vital roles of folate exhibits in three ways: the unique methyl donor for DNA expression regulation, the de novo biosynthesis of purine and pyrimidine for DNA construction, and the serum homocysteine removal. Thymidylate synthase (TYMS) is the solo catalysis enzyme for the de novo synthesis of dTMP, which is the essential precursor of DNA biosynthesis and repair process. To examine the role of TYMS in Congenital Cardiac Septal Defects (CCSDs) risk, we investigated whether genetic polymorphisms in the TYMS gene associated with the CCSDs in a Han Chinese population.

Method

Polymorphisms in the noncoding region of TYMS were identified via direct sequencing in 32 unrelated individuals composed of half CCSDs and half control subjects. Nine SNPs and two insertion/deletion polymorphisms were genotyped from two independent case-control studies involving a total of 529 CCSDs patients and 876 healthy control participants. The associations were examined by both single polymorphism and haplotype tests using logistic regression.

Result

We found that TYMS polymorphisms were not related to the altered CCSDs risk, and even to the changed risk of VSDs subgroup, when tested in both studied groups separately or in combination. In the haplotype analysis, there were no haplotypes significantly associated with risks for CCSDs either.

Conclusion

Our results show no association between common genetic polymorphisms of the regulatory region of the TYMS gene and CCSDs in the Han Chinese population.     

The polymorphisms of Tim-1 promoter region are associated with rheumatoid arthritis in a Korean population

It has been determined that the family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is expressed on T cells. A member of the TIM family, TIM-1, is considered to be a membrane protein associated with the development of Th2-biased immune responses and selectively expressed on Th2 cells. We previously showed that the exon 4 variations of Tim-1 are associated with susceptibility to allergic diseases, as well as autoimmune diseases such as rheumatoid arthritis (RA). In this study, we assessed the association between genotype and allele frequencies of the Tim-1 gene promoter region, in both RA patients and the controls without RA, using polymerase chain reaction-restriction fragment length polymorphism and single-base extension methods. We further investigated the relationships among the genotypes of each polymorphism and C-reactive protein or rheumatoid factor levels in RA patients. The genotype and allele frequencies of the –1637A>G polymorphism in RA patients are significantly different from those in the non-RA controls (P=0.0004 and P=0.001, respectively). Our results strongly suggest that polymorphism in the Tim-1 promoter region might be associated with susceptibility to RA.     

Dopamine D1 receptor gene polymorphism is associated with myocardial infarction

Dopamine D1 receptor (DRD1) gene is associated with the pathogenesis of myocardial infarction (MI) in aspects of plaque rupture, platelet aggregation, and neutrophil-mediated injury of cardiac myocytes. Thus, the study was designed to explore whether the A-48G polymorphism of the DRD1 gene was associated with MI. The genotype of the DRD1A-48G polymorphism was determined by polymerase chain reaction in the 602 Han Chinese participants, 255 MI patients and 347 controls without MI. A significant association was found between the A-48G polymorphism of DRD1 and MI (genotype model: χ(2)=13.2, unadjusted p=0.001; χ(2)=13.9, adjusted p=0.0002; dominant model: adjusted OR 2.05, 95%CI 1.40-3.00, p=0.0002; recessive model: adjusted OR 2.34, 95%CI 1.01-5.39, p=0.047). The G allele was a risk-increased allele for MI (unadjusted OR 1.83, 95%CI 1.34-2.50, p=0.0001; adjusted OR 1.94, 95%CI 1.40-2.68, p=0.00007). Thus, the study demonstrated the significant association between A-48G polymorphism of the DRD1 gene and MI.     

汉族人群中22个HLA-Cw等位基因全长序列单核苷酸多态性分析

为探讨HLA-Cw (Human leukocyte antigen-Cw)基因全长序列分子遗传多态性, 文章对28个HLA-Cw基因型已知的汉族个体样本, 采用长距离PCR技术和高保真性的Pfu酶, 扩增HLA-Cw基因全长序列4.5 kb, 进行分子克隆和单倍体测序。采用群体遗传学研究方法分析了HLA-Cw等位基因全长序列中各亚区的单核苷酸多态性。结果表明: 在28个样本中共检测出22种等位基因, 序列均已提交GenBank和国际IMGT/HLA数据库并获得了认可; 其中Cw*0706、Cw*030301、Cw*140201的全长序列为首次报道, 尤其是Cw*0706内含子序列的获得, 能够重新设计对该等位基因测序分型的引物, 避免测序分型中可能对这一等位基因的漏检。将28个样本的56条单倍体序列用Clustal软件进行序列排比, 输入到DnaSP4.0进行多态性分析, 共发现244个SNPs, 10处插入/缺失多态性。对HLA-Cw等位基因各亚区多态性的分析, 发现第4内含子及以前并没有受到关注的第5外显子受到平衡选择的作用, 在进化中受到了选择压力, 预示着它们在免疫系统的进化过程中可能扮演着重要的角色。     

Peroxisome proliferator-activated receptor-gamma gene polymorphisms are not associated with osteonecrosis of the femoral head in the Korean population

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease to which certain individuals are more at risk. Altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. Peroxisome Proliferator-Activated Receptor-gamma (PPARgamma) plays a crucial role in differentiation of mesenchymal cells to adipocytes, lipid homeostasis, and bone metabolism. To investigate the possible association between PPARgamma gene variants and susceptibility to ONFH, we genotyped three common polymorphisms (-796A > G, +34C > G[Pro12Ala], and +82466C > T[His477His]) in 448 ONFH patients and 336 control subjects. Genotypes, allele frequencies, and haplotypes of the polymorphisms in the complete set of patients as well as in subgroups by sex or etiology were not significantly different from those in the control group. This suggests that the examined polymorphisms and haplotypes of the PPARgamma gene are unlikely to be associated with susceptibility to ONFH.     

Single nucleotide polymorphisms in chicken lmbr1 gene were associated with chicken growth and carcass traits

Lmbr1 is the key candidate gene controlling vertebrate limb development, but its effects on animal growth and carcass traits have never been reported. In this experiment, lmbr1 was taken as the candi-date gene affecting chicken growth and carcass traits. T/C and G/A mutations located in exon 16 and one A/C mutation located in intron 5 of chicken lmbr1 were detected from Silky, White Plymouth Rock broilers and their F2 crossing chickens by PCR-SSCP and sequencing methods. The analysis of vari-ance (ANOVA) results suggests that T/C polymorphism of exon 16 had significant association with eviscerated yield rate (EYR), gizzard rate (GR), shank and claw rate (SCR) and shank girth (SG); A/C polymorphism of intron 5 was significantly associated with SCR, liver rate and head-neck weight (HNW), while both sites had no significant association with other growth and carcass traits. These results demonstrate that lmbr1 gene could be a genetic locus or linked to a major gene significantly affecting these growth and carcass traits in chicken.     

Single nucleotide polymorphisms in the corticotrophin-releasing hormone and pro-opiomelancortin genes are associated with growth and carcass yield in beef cattle

A single nucleotide polymorphism (SNP) in the corticotrophin-releasing hormone gene (CRH C22G) alters the fourth amino acid in the signal sequence from proline to arginine. Two other SNPs (CRH A145G and C240G) occur in the propeptide region at residue positions 45 and 77, respectively, that result in serine/asparagine and histidine/aspartic acid substitutions respectively. These SNPs, as well as SNPs in pro-opiomelancortin (POMC), leptin (LEP) and melanocortin-4 receptor (MC4R), were evaluated for associations with average daily gain, end-of-test rib-eye area, shipping weight and hot carcass weight in a group of 256 steers using a general linear model. The CRH C22G SNP was associated with end-of-test rib-eye area (P < 0.034) and hot carcass weight (P < 0.0015). The SNP in POMC was associated with shipping weight (P < 0.0078) and hot carcass weight (P = 0.006) while it approached significance for average daily gain (P < 0.07). The SNP in MC4R approached significance for hot carcass weight (P < 0.085) while no significance was observed between the leptin SNP and the above listed traits. Because both CRH and POMC regulate appetite, potential interaction effects between these two genes were assessed. The absence of an interaction effect between CRH and POMC with hot carcass weight suggests that these genes act independently to increase carcass yield. These gene effects used singularly or together could result in an economic benefit to the beef industry.     

Single nucleotide polymorphisms in ABCG5 and ABCG8 are associated with changes in cholesterol metabolism during weight loss

The purpose of this study was to examine whether changes in cholesterol metabolism after weight loss were affected by single nucleotide polymorphisms (SNPs) in ABCG5 and ABCG8 genes. Thirty-five hypercholesterolemic women lost 11.7 +/- 2.5 kg (P < 0.001). Cholesterol kinetics were assessed using stable isotope techniques. TaqMan PCR was used to detect SNPs in ABCG5/G8. Homozygous Q604E variants in ABCG5 had larger (P < 0.05) reductions in cholesterol absorption and greater increases (P < 0.05) in synthesis in contrast to heterozygous and homozygous wild-type carriers. Heterozygous C54Y carriers had smaller declines (P = 0.047) in synthesis compared with homozygous variant individuals. The presence of at least one Y54 variant was associated with higher (P = 0.042) post-weight-loss synthesis compared with carriers of the C54 genotype. The direction of the results is consistent with cross-sectional studies on the effects of Q604E and C54Y polymorphisms on plasma cholesterol. SNPs in ABCG5/G8 were found to be associated with the response of cholesterol metabolism to weight loss. The evidence for associations between SNPs in ABCG5/G8 and various parameters of cholesterol metabolism indicates the potential effectiveness of establishing genetic screening tools to determine optimal lipid-lowering treatment routes for individuals during weight reduction.     

Single nucleotide polymorphisms associated with aggressive periodontitis and severe chronic periodontitis in Japanese

Periodontitis is a common inflammatory disease causing destruction of periodontal tissues. It is a multifactor disease involving genetic factors and oral environmental factors. To determine genetic risk factors associated with aggressive periodontitis or severe chronic periodontitis, single nucleotide polymorphisms (SNPs) in multiple candidate genes were investigated in Japanese. We studied 134 patients with aggressive periodontitis, 117 patients with severe chronic periodontitis, and 125 healthy volunteers without periodontitis, under case-control setting, and 310 SNPs in 125 candidate genes were genotyped. Association evaluation by Fisher's exact test (p < 0.01) revealed statistically significant SNPs in multiple genes, not only in inflammatory mediators (IL6ST and PTGDS, associated with aggressive periodontitis; and CTSD, associated with severe chronic periodontitis), but also in structural factors of periodontal tissues (COL4A1, COL1A1, and KRT23, associated with aggressive periodontitis; and HSPG2, COL17A1, and EGF, associated with severe chronic periodontitis). These appear to be good candidates as genetic factors for future study.     

Single nucleotide polymorphisms of estrogen receptor alpha in human renal cell carcinoma

Estrogens and their receptors (ERs) have been shown to play a role in various cancers. We hypothesize that polymorphisms and genotypic changes of the ERalpha gene are involved in renal cell carcinoma. To test this hypothesis, DNA samples from 113 cases of human renal cell cancer were analyzed by sequence-specific polymerase chain reaction to determine the genotypic frequency of six different polymorphic loci on ERalpha gene (codon 10 T-->C, codon 87 G-->C, codon 243 C-->T, codon 325 C-->G, codon 594 G-->A, and intron 1 C-->T). The relative risk of variant genotype was calculated by comparison with 200 healthy controls. The results of this study demonstrate that the distribution of genotypes on codon 10 differs between renal cancer patients and healthy normal controls (p<0.05). The relative risk of the genotype 10C/C was calculated as 2.51. No differences in genotypes were observed at all other loci. We also analyzed DNA from pairs of cancerous and normal tissues from 96 cases of human renal cell cancer to characterize genotypic changes at these loci. Genotypic changes were detected in nine cancer samples on exon 1 (codons 10 and 87) of ERalpha, although none were detected at other regions. The present study demonstrates for the first time that codon 10 polymorphism on exon 1 of ERalpha may be involved in renal cancer risk.     

Single nucleotide polymorphisms of NR3C1 gene and recurrent depressive disorder in population of Poland

Depressive disorder is a disease characterized by disturbances in the hypothalamo–pituitary–adrenal axis. Abnormalities include the increased level of glucocorticoids (GC) and changes in sensitivity to these hormones. The changes are related to glucocorticoid receptors gene (NR3C1) variants. The NR3C1 gene is suggested to be a candidate gene affecting depressive disorder risk and management. The aim of this study was to investigate polymorphisms within the NR3C1 gene and their role in the susceptibility to recurrent depressive disorder (rDD). 181 depressive patients and 149 healthy ethnically matched controls were included in the study. Single nucleotide polymorphisms were assessed using polymerase chain reaction/restriction fragment length polymorphism method. Statistical significance between rDD patients and controls was observed for the allele and genotype frequencies at three loci: BclI, N363S, and ER22/23EK. The presence of C allele, CC, and GC genotype of BclI polymorphism, G allele and GA genotype for N363S and ER22/23EK variants respectively were associated with increased rDD risk. Two haplotypes indicated higher susceptibility for rDD, while haplotype GAG played a protective role with OR_dis 0.29 [95 % confidence interval (CI) = 0.13–0.64]. Data generated from this study support the earlier results that genetic variants of the NR3C1 gene are associated with rDD and suggest further consideration on the possible involvement of these variants in etiology of the disease.