Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population

Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.     

Association of ��2-adrenergic receptor and insulin receptor substrate-1 polymorphisms with obesity in a Northern Indian population

BACKGROUND:

Imbalance in hormonal levels, regulated by host genetic factors, are known to be a major cause of obesity. Therefore, we aimed to evaluate association of genetic polymorphisms of β₂-adrenergic receptor (β₂-AR) and insulin receptor substrate-1 (IRS-1) with hormonal levels in northern Indian obese.

METHODS:

A total of 111 obese and 89 age matched non-obese subjects were studied after taking detailed clinical profile. Hormonal assays in serum/plasma for different hormones were done using IRMA and RIA kits. Genetic analysis of β₂-AR (-47 and -20, T to C) and IRS-1 (Arg972Gly) was done using PCR-RFLP.

STATISTICAL ANALYSIS:

Statistical analysis was performed by SPSS (version 11.5) software. All continuous variables were expressed as mean ± SD and tested by ANOVA test. Comparisons of categorical variables were assessed using X² tests or Fisher''s exact test. P-value <0.05 was considered as significant.

RESULTS:

Analysis showed that obese subjects had significantly higher value of blood pressure (systolic), WHR, leptin insulin and glucagon and lower value of GH. In β₂-AR (-47) T/C and IRS-1 Gly972Arg gene polymorphisms we did not found significant differences in genotype or allele frequencies. Moreover, none of the studied hormonal or metabolic parameters showed any association with the gene polymorphisms.

CONCLUSIONS:

Study reveals no significant association of β₂-AR (-47 and -20, T to C) and IRS-1 Gly 972 Arg polymorphisms with obesity in northern Indians.     

Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case–control and a family-based association study in a Chinese Han population

Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case–control study and in a family-based association study. Case–control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the ‘G’ allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the ‘A’ allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z =?1.882, P = 0.049; Z =?2.000, P = 0.045; Z =?2.319, P = 0.020; Z =?2.002, P = 0.045; Z =?2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.     

Association between nasal allergy and a coding variant of the Fc ε RI β gene Glu237Gly in a Japanese population

The gene for the beta-chain of the high-affinity receptor for IgE (Fc epsilon RI beta) has been proposed as a candidate gene for atopy. A coding variant Glu237Gly has been studied in various populations with asthma and atopy, and the results were controversial for association of the variant with atopy/asthma. Because nasal allergy is a more common atopic disease and shows less remission than asthma, we analyzed whether the Glu237Gly variant is correlated with nasal allergy. The study enrolled 233 patients with nasal allergy and 100 control subjects. Further, three subgroups were selected: patients with perennial nasal allergy (n=149), Japanese cedar pollinosis (n=189), and allergy to multiple allergens (n=45). The allele frequency of Gly237 in the controls and patients was 0.14 and 0.20, and the frequency of Gly237-positive subjects was 0.23 and 0.356, respectively. There was a significant association between Gly237-positivity and nasal allergy, perennial nasal allergy, Japanese cedar pollinosis, and allergy to multiple allergens. Among all 333 subjects we observed a significant relationship between Gly237 and elevated levels of serum total IgE (>250 IU/ml) and very high IgE (>1000 IU/ml). Among patients positive for a specific IgE, Gly237 was significantly associated with high IgE for house dust, mite, and Japanese cedar pollen. These results suggest that the Glu237Gly variant of the Fc epsilon RI beta gene is involved in the development of nasal allergy through the process for the production of both specific and nonspecific IgE antibodies.     

Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of DeBakey type III aortic dissection

To investigate the association of myosin heavy chain protein 11 (MYH11) and transforming growth factor β signaling-related gene polymorphisms with the susceptibility of DeBakey type III aortic dissection (AD) and its clinical outcomes. Four single-nucleotide polymorphism (SNPs) (MYH11 rs115364997, rs117593370, TGFB1 rs1800469, and TGFBR1 rs1626340) were analyzed in patients with DeBakey III AD (173) and healthy participants (335). Gene–gene and gene–environment interactions were evaluated using generalized multifactor dimensionality reduction. The patients were followed up for a median of 55.7 months. MYH11 rs115364997 G or TGFBR1 rs1626340 A carriers had an increased risk of DeBakey type III AD. MYH11, TGFB1, TGFBR1, and environment interactions contributed to the risk of DeBakey type III AD (cross-validation consistency?=?10/10, P?=?0.001). Dominant models of MYH11 rs115364997 AG?+?GG genotype (HR?=?2.443; 95%CI: 1.096–5.445, P?=?0.029), TGFB1 rs1800469 AG?+?GG (HR?=?2.303; 95%CI: 1.069–4.96, P?=?0.033) were associated with an increased risk of mortality in DeBakey type III AD. The dominant model of TGFB1 rs1800469 AG?+?GG genotype was associated with an increased risk of recurrence of chest pain in DeBakey type III AD (HR?=?1.566; 95%CI: 1.018–2.378, P?=?0.041). In conclusions, G carriers of MYH11 rs115364997 or TGFB1 rs1800469 may be the poor prognostic indicators of mortality and recurrent chest pain in DeBakey type III AD. The interactions of gene–gene and gene–environment are associated with the risk of DeBakey type III AD.

     

The importance of ERα and ERβ gene polymorphisms in PCOS

Estrogens act through binding to estrogen receptor α (ERα) and β (ERβ). Studies in knockout mice have shown that the absence of ERα leads to the polycystic ovary syndrome (PCOS) phenotype. Furthermore, the expression of ERβ gene is lower in follicles derived from women with PCOS compared with healthy women. The aim of this study was to investigate the importance of ERα and ERβ gene polymorphisms in PCOS. A cohort of 180 women with PCOS and 140 healthy controls were recruited, and the PvuII and XbaI polymorphisms of ERα, as well as, the AluI and RsaI polymorphisms of ERβ were genotyped. No difference was found in the distribution of these polymorphisms between patients and healthy controls. However, in PCOS women, carriers of TC and TT genotypes of PvuII polymorphism had lower fasting glucose to insulin ratio compared with carriers of CC genotype (p = 0.029). In addition, the presence of AA genotype of XbaI polymorphism was associated with lower levels of follicle-stimulating hormone (FSH) compared with the presence of AG and GG genotypes (p = 0.03). The association of ERα polymorphisms with insulin resistance indices and FSH levels emphasizes the importance of ERα as a genetic modifier of the PCOS phenotype.     

Association of PPARγ2 polymorphisms with carcass and meat quality traits in a Pietrain x Jinhua F2 population

The PPARγ2 gene is a key regulator of both proliferation and preadipocyte differentiation in mammals. Herein its genotype and allele frequencies were analyzed using PCR-SSCP in eight pig breeds (N = 416). Two kinds of polymorphisms of the PPARγ2 gene were detected, including a previously reported shift SNP A177G (Met59Val) in exon 1 and a novel silent mutation G876A in exon 5. The results revealed that European pig breeds carry a higher allele A frequency at the A177G locus and a fixed GG genotype at the G876A locus. Allele A at the G876A locus was only found in Jinhua pigs. The association between haplotype (A177G/G876A) and carcass and meat quality traits was analyzed in a Pietrain x Jinhua F2 population (N = 248). The PPARγ2 gene was found to be significantly associated with backfat thickness at the shoulder (p < 0.05), 6-7(th) ribs (p < 0.01), last rib (p < 0.01), gluteus medius (p <0.05) and ham weight (p < 0.01). Significant effects of different haplotypes on ham weight and backfat thickness at the 6-7(th) ribs, last rib, and gluteus medius were also observed.     

Association of polymorphisms in the β2-adrenoreceptor gene with higher levels of parasitic infection

The diminishing incidence of parasitic infection in westernised societies has been suggested to result in an increased prevalance of asthma. Asthma is a polygenic disease and genome screens have shown that genes on chromosome 5q31–33 are strongly linked to the disease. The gene for the β₂-adrenoreceptor is located in this region and two polymorphisms have been identified that result in amino acid changes at positions 16 (ArgGly) and 27 (GlnGlu). To determine whether these polymorphisms influence asthma and parasitic infection, a genotype/phenotype study has been performed on a cohort of 126 children from Coche Island in Venezuela. There is a high incidence of asthma on the island and intestinal helminthiasis is endemic. Genotyping for both polymorphisms was carried out by using the polymerase chain reaction and allele-specific oligonucleotide hybridisation. Genotype frequencies in this cohort were consistent with other studies and both polymorphisms were in significant linkage disequilibrium. Individuals who were homozygous for Arg16 had significantly higher levels of specific IgE to Ascaris lumbricoides (P=0.002), significantly higher A. lumbricoides egg counts (P=0.001) and significantly larger wheal sizes following skin-prick testing with A. lumbricoides allergen (P=0.008). There was no association between either polymorphism and total serum IgE or asthma in this population. A combination of mast cell degranulation and the lung migratory phase of A. lumbricoides larvae may result in bronchoconstriction in infected individuals. These results suggest that the Gly 16 allele confers resistance to high levels of parasitic infection in this population. An alternative explanation for the association is that it may be the result of linkage disequilibrium with other genes in the chromosome 5q31–33 region. Received: 25 November 1998 / Accepted: 30 January 1999     

Association of TNF-α promoter polymorphisms with the outcome of persistent HBV infection in a northeast Chinese Han population

Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.     

Association analysis of GABAA β2 and γ2 gene polymorphisms with event-related prefrontal activity in man

Gamma-aminobutyric acid (GABA)A-receptors play a crucial role in the generation of electroencephalogram (EEG) oscillations and evoked potentials (ERPs). The present association study was designed to test whether EEG and ERPs are modulated by genetic variations of the human GABAA beta2 (GABRB2) and gamma2 (GABRG2) genes on chromosome 5q33. The genotypes of two nucleotide substitution polymorphisms of the GABRB2 and GABRG2 genes were assessed in 95 psychiatrically healthy subjects of German descent. Neurophysiological phenotyping was performed with four factorized EEG/ERP parameters: EEG activation, anterior and posterior EEG synchronization, and event-related activity (N100/ P200-complex). No genotypic association was found for the GABRB2 nucleotide exchange polymorphism with any electrophysiological parameter. A significant association was found between the genotype of the intronic GABRG2 G-->A nucleotide exchange and the event-related N100/P200 (ANOVA: F=3.81; df=2; P=0.026). A comparison of homozygous subjects carrying either the G/G or A/A genotype of the GABRG2 polymorphism consistently revealed an even stronger difference in the effect-size (ANOVA: F=11.13; df=1; P=0.002). Post hoc analysis of this association with current density analysis in three-dimensional neuroanatomic Talairach space-time showed a reduction in the event-related signal power after 120 ms in the right dorsolateral prefrontal cortex. Taking into account the risk of false-positive association findings attributable to multiple testing, our results encourage further replication studies to examine the phenotype-genotype relationship of GABRG2 gene variants and event-related prefrontal activity.     

Association of IL-6 promoter and IFN-γ gene polymorphisms with acute rejection of liver transplantation

Liver transplantation is one of the most important therapies for end-stage liver diseases and is associated with major problems including infections and acute rejection. The outcome of transplantation can be determined by immune responses as a key role in response to the graft. Inflammatory and anti-inflammatory mediators especially cytokines influence the graft microenvironment. Th1 and Th2 immune responses in contrast to regulatory responses cause acute rejection or help graft survival. In this study, we evaluated the gene polymorphisms of IL-6 G-174C, TGF-β T + 869C, IL-4 C-590T, and IFN-γ T + 874A cytokines in liver transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C, TGF-β T + 869C and IFN-γ T + 874A polymorphisms and PCR-RFLP using AvaII restriction enzyme was done for IL-4 C-590T characterization in 70 liver transplant patients. Acute rejection episodes were diagnosed according to standard criteria. The analysis of the results showed that IL-6-174 GG genotype ( P = 0.009, OR = 4.333, 95% CI = 1.043–18.000), IL-6-174G allele (P = 0.011, OR = 5.273, 95% CI = 1.454–19.127) was more frequent and IFN-γ +874 TT genotype was less frequent (P = 0.043, OR = 0.143, 95% CI = 0.0118–1.190) in acute rejection than in non-rejection patients. TGF-β T + 869C and IL-4 C-590T frequencies were not significantly different (P > 0.05). According to the results, it can be conclude that IL-6 G-174C and IFN-γ T + 874A gene polymorphisms have predictive values for acute rejection after liver transplantation. High producer genotype of IL-6 is a genetic risk factor and IFN-γ is a protective factor for acute rejection development.     

Association of polymorphisms in transforming growth factor-β receptors with susceptibility to gastric cardia adenocarcinoma

Both transforming growth factor-β receptor I (TGFBR1) and receptor II (TGFBR2) are serine/threonine kinases and play important roles in TGF-β/Smads signal pathway. The case–control study was performed to evaluate the possible association of Int7G24A and *6A polymorphisms of TGFBR1 and G-875A polymorphism of TGFBR2 with susceptibility to gastric cardia adenocarcinoma (GCA) in a population of North China. Polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR methods were used respectively to detect the genotype of Int7G24A, *6A and G-875A in 468 GCA and 584 healthy controls. Immunohistochemistry method was used to determine the protein expression of TGFBR1 and TGFBR2. Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. There were no differences in the genotype distribution of TGFBR1 *6A polymorphism among cases and controls. However, A allele of Int7G24A significantly elevated the risk of developing GCA (adjusted OR = 1.34, 95% CI 1.03–1.87) and A allele of G-875A significantly decreased the risk of developing GCA (adjusted OR = 0.73, 95% CI 0.49–0.92). When stratified for TNM stage, A allele of Int7G24A and G-875A allele carriers had a 1.41-fold (95% CI 1.05–1.98) increased and a 0.70-fold (95% CI 0.47–0.92) decreased risk of stage III and IV gastric cardia adenocarcinoma. The protein expression of TGFBR1 and TGFBR2 in GCA was not correlated with genotypes of them. In conclusions, TGFBR1 Int7G24A and TGFBR2 G-875A polymorphisms may play important roles in the risk of GCA in North China.     

Association between selected cholesterol-related gene polymorphisms and Alzheimer’s disease in a Turkish cohort

Molecular Biology Reports - Numerous genetic evidence has pointed out that variations in cholesterol-related genes may be associated with an Alzheimer’s disease (AD) risk. We aimed to...     

Genetic association of IDE,POU2F1, PON1, IL1α and IL1β with type 2 diabetes in Pakistani population

A number of genes are known to be involved in glucose homeostasis. Mutations and polymorphisms in candidate genes may effect insulin production, action or resistance. This study was designed to report the association of genetic polymorphism with the type 2 diabetes (T2D) in Pakistani population. A total of 458 subjects (case n = 288, control n = 170) participated in the study. Nine single nucleotide polymorphisms were investigated in genes IDE (rs6583813 C>T, rs7910977 C>T), POU2F1 (rs3767434 A>T, rs10918682 A>T, rs2146727 A>G), WFS1 (rs734312 A>G), PON1 (rs854560 T>A), IL1α (rs1800587 C>T) and IL1β (rs1143634 C>T). Genotyping was performed by DNA sequencing after nested polymerase chain reaction of targeted regions. Results indicated that rs7910977 in IDE showed significant association with the development of T2D [P = 0.012, OR 1.677 (95 % CI 1.112–2.438)]. The rs10918682 in POU2F1 was associated with T2D [P < 0.001, OR 3.606 (95 % CI 2.165–6.005)]. The rs854560 in PON1was associated with incidences of T2D and increased the risk of cardiovascular complications [P = 0.031, OR 0.663 (95 % CI 0.455–0.965)] in diabetics. The rs734312 from WFS1 gene was associated with diabetes at genotype level (P < 0.01). Haplotype analysis of rs1800587–rs1143634 depicted CC haplotype increased the susceptibility to diabetes (P < 0.05). Haplotype GAA from rs2146727–10918682–rs3767434 was protective against diabetes (P < 0.01) and GGA exhibited the association with T2D (P < 0.01). Haplotype CT from rs6583813–rs7910977 was protective against diabetes (P = 0.02). Our study provided evidence to IDE, PON1, WFS1, POU2F1, IL1α and IL1β associated with T2D in Pakistanis.     

Associations of polymorphisms in the β2-adrenergic receptor gene with essential hypertension in Han Chinese population

The β2-adrenergic receptor (β2-AR) gene has been implicated in the pathogenesis of hypertension. However, the results have been conflicting. In this study, we performed a meta-analysis to assess the associations of 46A/G and 79C/G polymorphisms in β2-AR gene with hypertension risk in Han Chinese population. Published literature from PubMed, ISI Web of Science, Embase databases, CNKI, CBM and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95?% confidence interval (CI) was calculated using fixed- or random-effects model. Eleven studies (2,058 cases and 1,459 controls) for 46A/G polymorphism and eight studies (2,219 cases and 1,495 controls) for 79C/G polymorphism were identified. The results suggested that 46A/G polymorphism G allele might increase the risk of hypertension (GG vs. AA: OR?=?1.47, 95?% CI 1.20-1.82). However, no significant association was observed for 79C/G polymorphism (GG vs. CC: OR?=?1.05, 95?% CI 0.61-1.79). The results indicated that 46A/G polymorphism in the β2-AR gene was associated with hypertension susceptibility in Han Chinese population.     

Association of TNF-α and IL-10 polymorphisms with tuberculosis in Tunisian populations

Cytokine Th1/Th2 balance is known to play a key role in controlling Mycobacterium tuberculosis infection. Based upon the functional role of the TNF-α [-308 G(low)?→?A(high) (rs1800629)] and IL-10 [-1082 A(low)?→?G(high) (rs1800870), -819 T(low)?→?C(high) (rs1800871) and -592 A(low)?→?C(high) (rs1800872)] single nucleotide polymorphisms (SNPs) on production levels, we genotyped 76 patients with pulmonary tuberculosis (TB) (pTB), 55 patients with extrapulmonary TB (epTB) and 95 healthy blood donors by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -308 A allele was associated with increased risk susceptibility to epTB (OR?=?1.96; 95% CI, 1.04-3.71; P?=?0.024). The -1082 AG genotype was significantly associated with increased risk development of epTB (odds ratio [OR]?=?3.69; 95% confidence intervals [CI], 1.73-7.92; P corrected for the number of genotypes [Pc]?=?0.0003). By contrast, -1082 AA genotype appeared to be associated with resistance to pTB (OR?=?0.38; 95% CI, 0.19-0.74; Pc?=?0.006) and epTB (OR?=?0.22; 95% CI, 0.1-0.48; Pc?=?0.00006). High-producer IL-10 GCC haplotype seemed to be associated with 2.11-fold (95% CI, 1.28-3.46; Pc?=?0.003) and 2.57-fold (95% CI, 1.5-4.4; Pc?=?0.0006) increased susceptibility to pTB and epTB, respectively. Combination of TNF-α/IL-10 high producer genotypes was associated with increased 3.13-fold (95% CI, 1.23-8.05; Pc?=?0.028) susceptibility to epTB. However, combined TNF-α/IL-10 low producer genotypes appeared to have protect effect to pTB (OR?=?0.44, 95% CI, 0.21-0.89; Pc?=?0.04) and epTB (OR?=?0.26, 95% CI, 0.1-0.62; Pc?=?0.0028). Collectively, our results showed that analysed SNPs in the TNF-α and IL-10 gene polymorphisms play key role in susceptibility to or protection against TB development in Tunisian populations.     

Association of the FCRL3 gene with rheumatoid arthritis: a further example of population specificity?

Association of a functional promoter polymorphism mapping to the Fc receptor-like 3 (FCRL3) gene has recently been reported and replicated with rheumatoid arthritis (RA) in Japanese populations. The aim of this study was to investigate association of the FCRL3 gene with RA in UK subjects. DNA was available from 1065 patients with RA and 2073 population controls from the UK. Four single nucleotide polymorphism (SNP) markers (FCRL3-169*C/T (fclr3_3, rs7528684), fclr3_4 (rs11264799), fclr3_5 (rs945635), fclr3_6 (rs3761959)) all previously associated with RA in a Japanese population were genotyped in 761 RA samples and 484 controls. In the remaining samples, only the putative disease causal polymorphism, FCRL3-169*C/T, was tested. Genotyping was performed using either the Sequenom MassArray iPlex platform or a 5' Allelic discrimination assay (Taqman, ABI). Extensive linkage disequilibrium was present across the promoter SNPs genotyped (r² values = 0.60-0.98). Allele frequencies did not differ between RA cases and controls either for the putative disease causal polymorphism (odds ratio FCRL3-169*C allele = 0.97 (0.87-1.07), p = 0.51) or for the other SNPs tested. Similarly, no association was detected with RA using haplotype analysis or when stratification by shared epitope carriage or by presence of rheumatoid factor was undertaken. This study was powered to detect an effect size of 1.24 or greater for the FCRL3-169*C/T functional promoter polymorphism but no evidence for association was detected, suggesting that this gene will not have a substantial effect in determining susceptibility to RA in populations of Northern European descent.     

Association of TNF-α gene with spontaneous deep intracerebral hemorrhage in the Taiwan population: a case control study

Background  

Genetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH). Previous studies have shown that TNF-α gene variation was associated with risks of subarachnoid hemorrhage in multiple ethnicities. The present case-control study tested the hypothesis that genetic variations of the TNF-α gene may affect the risk of Taiwanese SDICH. We examined the association of SDICH risks with four single nucleotide polymorphisms (SNPs) within the TNF-α gene promoter, namely T-1031C, C-863A, C-857T, and G-308A.     

Angiotensin-converting enzyme gene polymorphisms and T2DM in a case�Ccontrol association study of the Bahraini population

Bahrain has one of the highest incidence rates of type 2 diabetes mellitus (T2DM). Development of diabetic nephropathy (DN) as a complication was noticed in some patients while absent in others. This interesting observation raises the role of certain genetic risk factors for the development of DN. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism was found to be associated with T2DM. While some patients have predisposition to DN in the population, others have negative association. The present case-control association study was designed to investigate the association of ACE I/D polymorphism in T2DM patients in Bahrain especially in those who developed DN. A total of 360 T2DM patients (110 with DN and 250 without DN) and 360 healthy (non-diabetic) age-matched subjects were recruited for this study for comparison. The presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was investigated using PCR-gel electrophoresis. The results show that the distribution of the homozygote DD genotype of the ACE gene was high among Bahraini T2DM patients compared to the healthy non-diabetic subjects. In addition, the distribution of the deletion (D) allele was high among Bahraini T2DM patients with DN when compared to the healthy non-diabetic subjects. However, there was no significant difference in the distribution of ACE I/D allele and genotypes between DN patients when compared to those T2DM patients without DN. The results obtained in this study are in closely agreement with some previous reports which show a strong association of ACE polymorphism with T2DM patients, yet not a risk factor for development of DN.     

Quantitative evidence of a silent gene P° of human red cell acid phosphatase in south Polish population

The distribution of red cell acid phosphatase types in 3244 unrelated Polish adults is reported. Gene frequencies P^a = 0.3594, P^b = 0.5643 and P^c = 0.0763 were obtained. In a forensic case of disputed paternity an apparent mother/child incompatibility respect to red cell acid phosphatase was found, the mother appearing as type B and the child as type A. Determination of acid phosphatase activity suggested the presence of a silent gene P°. The phosphatase levels were about half the values expected, as determined in 237 adults representing the different phenotypes.