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 study of the β2-adrenergic receptor gene polymorphisms and hypertension in the Northern Han Chinese

Background

The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population.

Methodology/Principal Findings

This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk.

Conclusions/Significances

We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.     

Structural characterization and promoter activity analysis of the γ-kafirin gene from sorghum

A genomic clone encoding the γ-kafirin gene from sorghum was isolated and sequenced. A 2938 bp sequenced fragment includes an intronless open reading frame of 636 nucleotides encoding a putative polypeptide of 212 amino acids. Comparison of the deduced amino acid sequence of γ-kafirin with the published sequences of γ-prolamins of maize, and Coix revealed highly conserved domains. The N-terminal region of these proteins contains the conserved hexapeptide PPPVHL, which is repeated eight times in γ-zein, four times in γ-kafirin and three times in γ-coixin. The number of PPPVHL repeats accounts predominantly for the differences in the molecular weights of γ-prolamins. Several putative regulatory sequences common to the γ-kafirin and γ-zein genes were identified in both the 5′ and the 3′ flanking regions. Putative GCN4-like regulatory sequences were found at positions ?192 and ?476 in the 5′ flanking region of γ-kafirin. In the 3′ noncoding region, three putative polyadenylation signals, two AATAAT and one AATGAA, were found at positions + 658, + 716, and + 785, respectively. In order to investigate the role of the putative GCN4-like motifs and other possible cis-acting element(s) of the γ-kafirin promoter, a series of deleted and chimeric promoter constructs were introduced into maize, Coix and sorghum tissues by particle bombardment. Histochemical analysis of β-glucuronidase (GUS) activity in different tissues indicated that the element(s) responsible for tissue specificity is probably located in the 285-bp proximal region of the promoter, while the remaining promoter sequence seems to carry the element(s) responsible for the quantitative response.     

Evolution of the β-globin gene cluster in man and the primates

The arrangement of primate β-related globin genes has been determined by restriction endonuclease mapping of genomic DNA from species ranging from prosimians to man. The arrangement of the entire ?γγδβ-globin gene cluster in the gorilla and the yellow baboon is indistinguishable from that of man. Restriction site differences between these species are consistent with a surprisingly low overall rate of intergenic DNA sequence divergence of approximately 1% in 5 million years. A new world monkey (owl monkey) has a single γ-globin gene, suggesting that the ^Gγ-^Aγ-globin gene duplication in man is ancient, and occurred about 20 to 40 million years ago. The β-globin gene cluster in the brown lemur, a prosimian, is remarkably short (about 20,000 base-pairs) and contains single ?-, γ- and β-globin genes. The γ- and β-globin genes in this animal are separated by a curious gene containing the 3′ end of a β-globin gene preceded by sequences related to the 5′ end of the ?-globin gene.     

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 IL1β and IL4 gene polymorphisms with nasal polyps in a Polish population

Imbalance between proinflammatory and anti-inflammatory cytokines may regulate the inflammatory reaction in the nasal polyps. Polymorphisms in the regulatory regions of the cytokines genes may influence their expression. The aim of this study was to investigate the relationship between an IL-1β and IL-4 promoter polymorphisms and nasal polyps. The C-511T promoter polymorphism of the IL-1β gene and C-590T promoter polymorphism of the IL-4 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 208 Polish patients with nasal polyps and 200 healthy Polish subjects. The risk of susceptibility to NP was significantly higher in patients with NP who had ?511 T/T genotype of IL1β than in controls (OR 3.07; 95 % CI 1.18–7.99). No statistically significant differences were found between NP patients and the control group with regard to genotype distribution and allele frequencies of C/T polymorphism of IL4 gene. Our study demonstrated that the TT genotype for C-511T mutation associated with the risk of developing NP in a Polish population.     

Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene × gender interaction

The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes. We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P?<?0.05). SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples (P?=?0.0105). The T–A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample (P?=?0.012). Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample (P?<?0.05) and the best signal was rs1927796 (P?=?0.00858). In addition, rs7331762 showed a strong gene × gender interaction (P?=?0.00956) for obesity while rs1927796 showed a strong gene × gender interaction (P?=?0.000625) for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.     

Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were studied in T2DM patients as well as in normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) using suitable primers. The genotypic, allelic and carriage rate frequency distribution in patients and controls were analyzed by SPSS (version 15.0). Odd ratios with 95 % confidence interval was determined to describe the strength of association by logistic regression model. Double and triple combinations of genotypes were analyzed by χ² test. Gene–gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually, IL-6, TNF-α and IL-10 did not show any association. In double combination, IL-6 ?597 GA and TNF-α ?308 GG genotypes increased the risk up to 21 times and in triple combination IL-6 ?597 AA, TNF-α ?308 GG and IL-10 ?592 CA increased the risk of T2DM up to 314 times. In gene–gene interaction allele ‘A’ of all studied polymorphisms increased the risk of T2DM up to 1.41 times. Our results suggest that individuals having a haplotype combination of AA, GG and CA for IL-6, TNF-α and IL-10 gene polymorphisms will have higher susceptibility and be at greater risk of developing T2DM.     

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 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.     

DNA polymorphisms in north Sardinian newborns and their linkage with abnormal γ globin gene arrangements and with βo-thalassemia

Fetal hemoglobin analysis and globin gene mapping have identified one type of beta(0)-thalassemia and four different gamma globin gene arrangements among newborn babies from the northern part of Sardinia. The beta(0)-thalassemia with a nonsense mutation at codon 39 was found on two chromosomes, each with a distinct pattern of polymorphic restriction sites; one had the A gamma T (A gamma 75 Ile----Thr) mutation, while the second did not. Four closely related haplotypes were identified for chromosomes with the A gamma T mutation. The gamma-thalassemia heterozygosity with the -GA gamma- hybrid gene fell into two categories. One apparently originated through crossing-over between mismatched chromosomes characterized by the most common haplotype, while the other had polymorphisms resembling those of a less frequently occurring chromosome. Chromosomes with the -G gamma-AG gamma-A gamma- triplication had polymorphic sites to be expected for this condition, being complimentary to the -GA gamma- thalassemias. Of the two additional gamma globin gene variations the -G gamma- G gamma- arrangement was associated with the chromosome with the most commonly occurring haplotype, while the chromosome with the -A gamma-A gamma- arrangement had a haplotype characteristic for that with the A gamma T mutation, which identified an -A gamma-A gamma T- arrangement. The incidental discovery of a silent beta-chain mutant, Hb Hamilton, with the Val----Ile substitution at position beta 11, in five newborns was also reported.     

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.

     

Association of β-fibrinogen gene −148C/T and −455G/A polymorphisms and coronary artery disease in Chinese population: A Meta analysis

The purpose of our study was to evaluate the correlation between the β-fibrinogen gene −148C/T and −455G/A polymorphisms and susceptibility to coronary artery disease in the Chinese population using a meta-analytic approach. Eligible studies about this correlation were identified by searching the PubMed, EMBASE, and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls) involved the −148C/T polymorphism and 9 (with 1023 cases and 1081 controls) involved the −455G/A polymorphism. No publication bias was detectable and heterogeneity testing found significant differences between the ORs for both groups of studies. The combined OR for the 7 studies on susceptibility to coronary artery disease in −148T allele carriers compared to the −148C/C wild-type homozygotes was 1.31 (95%CI: 0.94–1.84, P=0.11). The combined OR for the 9 studies on susceptibility to coronary artery disease in −455A allele carriers compared to the −455G/G wild-type homozygotes was 1.75 (95%CI: 1.24–2.46, P=0.001). Our results suggest the absence of an association between the β-fibrinogen gene −148C/T polymorphism and susceptibility to coronary artery disease and the possibility that −455G/A polymorphism (in particular, allele A) increases susceptibility to this disease in the Chinese population.     

DNA polymorphisms in the ε- and γ-globin gene regions in asian macaques

DNA polymorphisms in the ε- and γ-globin gene regions in nine Asian macaques(Macaca fuscata, M. mulatta, M. nemestrina, M. cyclopis, M. fascicularis, M. arctoides, M. radiata, M. maura, andM. assamensis) were examined using several different restriction endonucleases and the human ε and γIVS2 probes.M. fuscata andM. mulatta had highly polymorphic sites(BglII andHincII, respectively) in the ε-globin gene region. TheBamHI site in the γ-globin gene region was highly polymorphic inM. mulatta, while theBglII andHindIII sites in the γ-globin gene region were highly polymorphic inM. fuscata andM. mulatta. The presence of the γ-globin gene triplication was frequently observed inM. fuscata. The gain or loss of an additionalBglII site between two γ-globin genes in Asian macaques seems to be very meaningful for discussing genetic relationships among them. This study was supported in part by the Cooperation Research Program of the Primate Research Institute, Kyoto University.     

Association of α-adducin and G-protein β3 genetic polymorphisms with hypertension: a meta-analysis of Chinese populations

Background

Mounting evidence has suggested that α-adducin and G-protein β3 (GNB3) genes are logical candidates for salt-sensitive hypertension. Some, but not all, studies have reported that α-adducin G460T and GNB3 C825T polymorphisms may influence the risk of the disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the influence of these two polymorphisms on hypertension and potential biases in Chinese.

Methods

Data were analyzed using Stata (v11.0) and random-effects model was applied irrespective of between-studies heterogeneity, which was evaluated via subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger''s test and funnel plot.

Results

36 study populations totaling 9042 hypertensive patients and 8399 controls were finally identified. Overall, in allelic/genotypic/dominant/recessive models, no significant association was identified for both G460T and C825T polymorphisms (P>0.05) and there was possible heterogeneity (I ²>25%). Subgroup analyses by study design indicated that the magnitude of association in population-based studies was marginally significantly strengthened for α-adducin G460T allelic model (OR = 1.12; 95% CI: 1:00–1.25; P = 0.043). Moreover, subgroup analyses by geographic distribution indicated comparison of 825T with 825C yielded a marginally significant increased risk in southern Chinese only (OR = 1.48; 95% CI: 1.01–2.16; P = 0.045). Further meta-regression analyses showed that geographic regions were a significant source of between-study heterogeneity for both polymorphisms. There was a possibility of publication bias for G460T, but not for C825T.

Conclusions

Our overall results suggest null association of α-adducin G460T and GNB3 C825T polymorphisms with hypertension in Chinese but indicate local marginal significance of C825T, as a putative salt-sensitive switch, in southern Chinese.     

Association of polymorphisms and haplotypes in the 5′ region of COLIA1 gene with the risk of osteoporotic fractures in Russian women from Volga-Ural region

The analysis of ?1997G/T, ?1663indelT, and +1245G/T polymorphic loci of the 5′-region of COLIA1 gene in 124 females aged from 50 to 70 years old with low numbers of traumatic fractures as well as 150 healthy individuals from Volga-Ural region has been conducted. The association of ?1663indelT and +1245G/T loci with the risk of osteoporotic fractures has been discovered. It has been shown that ?1997*G*G/?1663*I*D/+1245*G*T genotype combination and ?1997*G/?1663*D/+1245*T haplotype can be considered as markers for fracture development.     

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.