Allele Of Intron Research Articles

Association of surfactant protein B gene polymorphisms (C/A-18, C/T1580, intron 4 and A/G9306) and haplotypes with bronchopulmonary dysplasia in chinese han population

SummaryThis study aimed to investigate the association between surfactant protein B (SP-B) polymorphisms and bronchopulmonary dysplasia (BPD) in Chinese Han infants. We performed a casecontrol study including 86 infants with BPD and 156 matched controls. Genotyping was performed by sequence specific primer-polymerase chain reaction (PCR) and haplotypes were reconstructed by the fastPHASE software. The results showed that significant differences were detected in the genotype distribution of C/A-18 and intron 4 polymorphisms of SP-B gene between cases and controls. No significant differences were detected in the genotype distribution of C/T1580 or A/G9306 between the two groups. Haplotype analysis revealed that the frequency of A-del-C-A haplotype was higher in case group (0.12 to 0.05, P=0.003), whereas the frequency of C-inv-C-A haplotype was higher in control group (0.19 to 0.05, P=0.000). In addition, a significant difference was observed in the frequency of C-inv-T-A haplotype between the two groups. It was concluded that the polymorphisms of SP-B intron 4 and C/A-18 could be associated with BPD in Chinese Han infants, and the del allele of intron 4 and A allele of C/A-18 might be used as markers of susceptibility in the disease. Haplotype analysis indicated that the gene-gene interactions would play an important part in determining susceptibility to BPD.

A Patient With Pancreas Divisum, Recurrent Acute Pancreatitis, and Homozygosity for the Cystic Fibrosis Transmembrane Regulator–Associated Protein 5T Allele

Mutations in the gene encoding the cystic fibrosis transmembrane regulator (CFTR) have been reported to increase the risk of recurrent acute pancreatitis in patients with pancreas divisum. We assessed the CFTR gene in a young male patient with pancreas divisum and recurrent acute pancreatitis. Magnetic resonance cholangiopancreatography and computed tomography revealed that the patient had pancreas divisum, with an enlarged and tortuous pancreatic duct; he also had positive results from the cystic fibrosis sweat test. Genetic analysis did not identify any common CFTR mutations, but did show that he was homozygous for the 5T allele in intron 8 IVS8 5T-12TG (which affects splicing at intron 8). Endoscopic sphincterotomy and stenting of papilla minor was performed. The IVS8 5T-12TG variant has been associated with abnormal organ development, therefore it is possible that CFTR has an important role in the development of the pancreatic duct. We propose this patient has recurrent acute pancreatitis resulting from a developmental defect associated with a suboptimal CFTR function.

Association of intronic repetition of SLC26A4 gene with Hashimoto thyroiditis disease

Intronic microsatellites repeats were implicated in the pathogenic mechanisms of several diseases. SLC26A4 gene, involved in the genetic susceptibility of autoimmune thyroid disease (AITD), harbours large non-coding introns. Using the tandem repeat finder (TRF) Software, two new polymorphic microsatellite markers, rs59736472 and rs57250751, located at introns 10 and 20, respectively, were identified. A case-control design including 308 patients affected with AITD (146 GD, 90 HT and 72 PIM) and 212 unmatched healthy controls were performed for each marker (rs59736472, D7S2459 and rs57250751). Furthermore, we used PHASE 2.0 version to reconstruct haplotypes, Kolmogorov-Smirnov (KS) and the Clump analysis program for multivariate analysis. The fluorescent genotyping revealed three alleles (106,112 and 115 bp) for rs57250751 and 12 alleles for both D7S2459 and rs59736472 ranging from 134 to 156 bp and from 144 to 168 bp, respectively. The case-control analysis confirmed the positive association of D7S2459 with Hashimoto thyroiditis (HT) disease previously reported. Moreover, a significant association was found only with rs59736472 and HT disease. Haplotype-specific analysis showed that the 140-148-115 haplotype may increase the risk of HT (χ2=9.8, 1 df, P=0.0017, OR=2.07, IC [1.27-3.36]). Consequently, considering the number of repetitions of both D7S2459 and rs59736472, we found 15 alleles ranging from 45 to 59 repetitions. The case-control analysis showed a significant association of the 55 repetition with HT disease (χ2=6.32, 1 df, p c=0.012, OR=1.74, IC [1.1-2.76]). In conclusion, we suggest the association of longer alleles of intron 10 of SLC26A4 gene with HT disease.

Polymorphisms of CYP19A1 and response to aromatase inhibitors in metastatic breast cancer patients

Single nucleotide polymorphisms (SNPs) in the gene encoding aromatase (CYP19A1) have been associated with differential benefit from letrozole treatment in metastatic breast cancer (mBC) patients, but validation is lacking. The aim was to investigate whether polymorphic variation of CYP19A1 and enzymes involved in estrogen and aromatase inhibitors (AIs) metabolism are associated with efficacy of AIs. 308 Women with estrogen-receptor-positive metastatic mBC treated with a third-generation AI were identified retrospectively. DNA was extracted from archival formalin-fixed paraffin embedded tumors and genotyped for 71 variants in 16 candidate genes, including CYP19A1. Time to treatment failure (TTF) was significantly improved in patients carrying the minor (T) allele of rs4775936 when compared to patients with the reference allele [HR = 0.79 per T allele (0.66-0.95); P = 0.012]. Patients with >7 TTTA repeats on either allele of CYP19A1 intron 4 had a lower risk of failure than those with a smaller repeat size [HR = 0.84 per >7 TTTA repeats (0.7-0.99); P = 0.04]. However, importantly in multivariate analysis, adjusting for the number of disease sites; disease-free interval from diagnosis to first recurrence, grade at diagnosis and first recurrence type neither variant maintained independent predictive significance. None of the 56 SNPs analyzed as an exploratory set showed significant association with TTF. Variants in CYP19A1 or other selected genes associated with AI metabolism were not independently associated with improved AI efficacy and emphasize the importance in pharmacogenetic studies of considering genetic biomarkers in the context of relevant prognostic factors.

Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.

Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population.

Genetic variation in nucleotide excision repair pathway genes influence prostate and bladder cancer susceptibility in North Indian population

BACKGROUND:Inherited polymorphisms of XPD and XPC genes may contribute to subtle variations in NER DNA repair capacity and genetic susceptibility to development of urological cancer such as prostate and bladder cancer.MATERIALS AND METHODS:We genotyped four Single Nucleotide Polymorphs (SNPs) of the DNA repair gene XPD and XPC in 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 healthy controls from the same area. XPD Exon 10 (G>A) by amplification refractory mutation system and Exon 23 (A>C), XPC Intron 9 (Ins/Del) and Exon 15 (A>C) were genotyped by PCR-RFLP.RESULTS:Variant genotype of XPC demonstrated association with PCa as well as in BC (P, 0.013; P, 0.003). Combined genotype (GA+AA) revealed association with PCa and in BC (P, 0.012, P, 0.002). Variant allele also demonstrated risk in both the cancer. Diplotype of XPD and XPC was associated with a significant increase in PCa and BC risk. Variant (+/+) genotype of XPC intron 9 shown increased risk with PCa and in BC (P, 0.012; P, 0.032). CC genotype of XPC exon 15 revealed increase risk (P, 0.047) with PCa not in BC. In clinopathological grade variant allele of XPC intron 9 and 15 demonstrated risk with high grade of tumor and bone metastasis of PCa. In BC variant allele of XPD exon 10 and 15 also shown association with tumor grade. XPC intron 9 influences the risk of BC in former tobacco users in BC.CONCLUSIONS:Our result support that SNPs in XPD and XPC gene may reduce NER repair capacity and play a major role for PCa and BC in North India.

Cryptic introgression between murre sister species (Uria spp.) in the Pacific low Arctic: frequency, cause, and implications

As southern species undergo northward range expansions, reports of hybridization between temperate and arctic taxa are increasing, which may have important implications for the evolution, conservation, and management of arctic species. The extent of hybridization between temperate common murres (Uria aalge) and arctic thick-billed murres (U. lomvia), seabirds in the family Alcidae, has been the subject of debate. In a previous survey of variation in mitochondrial DNA (mtDNA) in common and thick-billed murres sampled from throughout the North Pacific and low Arctic, 12 of 327 common murres (~4%) were found to possess DNA sequences characteristic of thick-billed murres. In the present study, we surveyed variation in three nuclear introns in 230 common murres and 56 thick-billed murres and report that these putative hybrids carry various combinations of intron alleles from common and thick-billed murres. Analysis using the program STRUCTURE indicated that nine of these individuals possessed high proportions of thick-billed murre intron alleles, two possessed alleles in F1 and F2 proportions, and one individual possessed predominantly common murre intron alleles. We propose that the asymmetric mtDNA introgression we observed is most likely the result of mate choice at mixed colonies based on differences in male mating behaviours. Our results highlight that hybridization between thick-billed and common murres is more prevalent than previously thought, which may have important implications for the conservation and management of arctic-dwelling thick-billed murres as common murres expand northward.

CYP2B6 Polymorphisms Influence the Plasma Concentration and Clearance of the Methadone S-Enantiomer

Methadone is a racemic compound composed of the R-form and S-form enantiomers. The drug is usually used in maintenance therapy for the heroin-addicted patients. In our previous study, we found that the cytochrome P-450 (CYP) isozyme 2B6 preferentially metabolizes the S-methadone enantiomer. We thus tested whether CYP2B6 gene polymorphisms had any influence on the concentration or clearance of methadone. Ten single nucleotide polymorphisms within this gene region were evaluated in 366 patients undergoing methadone maintenance for at least 3 months. The plasma steady-state levels of racemic methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine were then measured in these individuals. The rs10403955 (T allele in intron 1), rs3745274 (G allele in exon 4), rs2279345 (T allele in intron 5), and rs707265 (A allele in exon 9) CYP2B6 allele types were found to be significantly associated with a higher clearance, a lower plasma concentration, and a lower concentration-to-dosage (C/D) ratio of (S)-methadone (P < 0.0017). Two haplotype blocks of a trinucleotide haplotype (rs8100458-rs10500282-rs10403955 in intron 1) and a hexanucleotide haplotype (rs2279342-rs3745274-rs2279343-rs2279345-rs1038376-rs707265 from intron 2 to exon 9) were constructed within CYP2B6. The major combinations of T-T-T and A-G-A-T-A-A of these particular haplotypes showed significant associations with the plasma concentrations of S-methadone and its C/D ratio (P < 0.0001, respectively). We conclude that genetic polymorphisms in the CYP2B6 gene may therefore be indicators of the clearance, plasma concentration and C/D ratio of S-methadone.

Allelic polymorphism in the serotonin transporter gene in major depression patients*

Introduction: Major depression (MD), like other mood disorders, is considered a worldwide endemic pathology, becoming one of the biggest public health problems. The hereditary factors of mood disorders have been studied for many years and different chromosomal regions and genes have been involved in this physiopathological process. Objective: To establish the association between allelic variants of the serotonin transporter gene (5-HTTLPR and VNTR) and MD in a population with this diagnostic in the department of Caldas, Colombia. Materials and methods: A case-control study was conducted with individuals older than 16 years of age born in the department of Caldas. The sample was composed of 59 patients with the MD with family antecedents of the pathology and 59 controls paired by precedence, age, and gender. For the cases and controls selection the Diagnostic Interview for Genetic Studies (DIGS) was used. Using the Hranilovic et al. protocol, the polymorphic regions in the promoter and third intron of the Serotonin Transporter gene was amplified. Results: It was not possible to find association between MD and the genetic or clinical variables. The absence of the short allele of the promoter could act as a protective factor (OR=0.70 CI 95%=0.313 to 1.604), for the development of the pathology in this population, and the presence of at least one copy of the 10 repetition alleles of the third intron could act as a risk factor (OR: 1.25), but the wide confidence interval (CI 95%=0.38 to 2.64) does not permit supporting these conclusions. Discussion: The results obtained in this population do not yield conclusive information related with the etiopathogeny of MD, but do not contradict those obtained in other studies with bigger samples than ours. The broad confidence interval does not support conclusions about the role as a risk factor for the 10 repetition alleles of the intron or the absence of the S allele of the promoter as a protector factor. Further studies with larger population samples may help to clarify these facts.

Polymorphisms in the endothelial nitric oxide gene are associated with lower vascular reactivity after a maximal dynamic exercise

Our aim was to investigate the influence of three polymorphisms in the endothelial nitric oxide (eNOS) gene (−786T>C, intron 4b4a and 894G>T), on the vascular reactivity (VR) to an ischemic stimulus. We evaluated 106 healthy, sedentary, non-obese women (31 ± 9 years). Genotypes were determined by PCR-RFLP and haplotypes inferred based on the Bayesian method. VR was considered the change in forearm vascular conductance [blood flow (plethysmography) divided by mean blood pressure (auscultation); ml/100ml.min.100mmHg] provoked by 5 min of ischemia before, 10 and 60 min after a maximal cardiopulmonary exercise test (CPET). VR increased 10 min after the CPET in the entire sample (p<0.001 vs. baseline). Subjects with polymorphic alleles at position −786 and intron 4 had a trend for lower VR 10 min after the CPET versus wild type counterparts (−786CC: 7.7 ± 1.5 vs. −786TT: 10.1 ± 0.6, p = 0.06; 4b4a/4a4a: 8.5 ± 5.9 vs. 4b4b: 10.0 ± 0.5, p = 0.06). In addition, a haplotype with polymorphic alleles at positions −786 and 894 (−786C/4b/894T; 8.9 ± 0.7) and another with polymorphic allele in intron 4 (−786T/4a/894G; 7.5 ± 1.3) had lower VR 10 min after the CPET versus a haplotype with wild type alleles (−786T/4b/894G; 10.1 ± 0.4, p = 0.02 and 0.05, respectively). Thus, these results suggest that the −786T>C, intron 4b4a and 894G>T polymorphisms are associated with lower VR after a maximal dynamic exercise. Support: CAPES, CNPq and FAPERJ.

The Genetic Role of Cyclooxygenase 2 in Ureter Cancer in Taiwan

The association between cyclooxygenase 2 (Cox-2) and ureter cancer has never been investigated in the past. In this study, the association of Cox-2 genotypic polymorphisms with ureter cancer was examined to specifically address this issue. Fifty-six ureter cancer patients and 436 non-cancer controls recruited from the China Medical Hospital in central Taiwan were genotyped and analyzed. Up to six polymorphic variants of Cox-2, including G-1195A, G-765C, T+8473C, intron 1, 5, and 6, were investigated in our study to analyze the association of the genotypes with susceptibility to ureter cancer. At first, no significant difference in the distribution between the ureter cancer and control groups was found in each of the polymorphism site investigated. However, our analysis of the joint effect for Cox-2 G-765C and intron 6 showed that individuals with GC at G-765C and AG+AA at intron 6 presented a higher potential for developing ureter cancer than the other groups. Since there was no obvious association between Cox-2 genotypes and ureter cancer stage or grade, our findings suggest that the C allele of Cox-2 G-765C together with the A allele of intron 6 may be responsible for ureter carcinogenesis and may be useful in the early detection and prediction of ureter cancer.

Tracing the origin of ‘blue Weimaraner’ dogs by molecular genetics

Weimaraner dogs are defined by light brown coat colour termed grey including several shadings ranging from silver and deer to mouse grey. In contrast, the so-called blue Weimaraners (BW) with lightened black-pigmented coat have been proposed to represent spontaneous revertants in the Weimaraner breed. In order to investigate the genetic determinants of the characteristic grey coat colour versus those of BW, known variation in coat colour genes including TYRP1 and MLPH were analysed in a number of grey and blue dogs. Variations at the B locus cause grey coat colour in Weimaraners via two non-functional TYRP1 copies (bb) including the b(s), b(d) and b(c) alleles. In all BW, at least one functional TYRP1 allele (Bb or BB genotype) was identified. Defined microsatellite alleles in TYRP1 intron 4 are linked to this functional B allele in BW. These alleles were also detected in various other dog breeds, but not in grey Weimaraners. The combination of a dominant trait for blue versus grey together with a specific TYRP1 haplotype in BW suggests that blue coat colour is not the result of spontaneous (back-) mutation in grey Weimaraners. This inference is even emphasized by the presence of a unique Y-chomosomal haplotype in a male offspring of the supposed ancestor of the BW population which - according to pedigree information - carries a copy of the original Y chromosome. Thus, molecular genetic analyses of coat colours combined with Y-chromosomal haplotypes allow tracing the origin of atypical dogs in respective canine populations.

Association Between Hepatitis B Viral Burden in Chronic Infection and a Functional Single Nucleotide Polymorphism of the PDCD1 Gene

PD-1, encoded by PDCD1, is highly expressed on virus-specific T cells and plays critical roles in modulating anti-virus immune responses in chronic viral infection. It is unknown, however, whether polymorphisms of the PDCD1 are associated with viral clearance during chronic viral infections. Here, we used the polymerase chain reaction-restriction fragment length polymorphism method to genotype two single nucleotide polymorphisms (SNPs) of PDCD1 in 502 patients with chronic hepatitis B virus (HBV) infection and 359 healthy controls to determine the association between PDCD1 genotypes and serum viral load as well as the risk of chronic infection. Our results showed that although neither the P7209(C/T) SNP site nor the P8737(A/G) site was associated with the risk of chronic HBV infection, the P7209 (T) allele in intron 4 is significantly associated with lower viral burden in the blood. Using a luciferase reporter assay, we demonstrated that the P7209 (T) allele creates a negative cis-element for gene transcription. Our data provide the first evidence that PDCD1 polymorphisms is a genetic factor in pathogenesis of chronic viral infection and reveal the functional significance of the P7209 SNP of the PDCD1.

Variation in the PPARα gene in Polish rowers

The PPARα gene code for transcriptional factor that is a central regulator of expression of genes involved in fatty acid metabolism and is believed to be a one of the genes of health-related fitness phenotype. The aim of this study was to examine the hypothesis that G allele of PPARα intron 7 G/C polymorphic site (rs4253778) is positively associated with endurance athlete status. PPARα genotypes were analyzed for 55 Polish rowers: 30 elite rowers representing the highest national competitive standard and 25 non-elite rowers representing regional standard. Control samples were prepared from 115 unrelated volunteers. The G/C polymorphic site in PPARα intron 7 was scanned by using PCR-RFLP protocol with TaqI enzyme. The allele frequency and genotype distribution was determined by gene and genotype counting. Significance was assessed by χ 2 analysis. The obtained results revealed that frequency of the PPARα GG genotype (87% vs. 63%; p = 0.04) and G allele (93% vs. 79%; p = 0.009) were significantly higher in the elite group of the Polish rowers compared to sedentary controls. These data confirm that GG genotype is more prevalent in the group of endurance athletes therefore G allele may be considered as one of the endurance-related allele.

Polymorphic Variants of DNA Repair Gene XRCC3 and XRCC7 and Risk of Prostate Cancer: A Study from North Indian Population

DNA repair gene alterations may cause a reduction in DNA repair capacity and influence an individual's susceptibility to carcinogenesis. We hypothesized that single nucleotide polymorphisms of DNA repair genes may be a risk factor for prostate cancer (PCa) susceptibility, influencing expression of homologous recombination (XRCC3) and nonhomologous end-joining (XRCC7) genes and conferring predisposition to PCa. In a case-control study, genotyping was done in 192 patients with PCa and 224 age matched unrelated healthy controls of similar ethnicity to determine variants in XRCC3 Exon 7 (C18067T, rs861539), IVS5-14 (A17893G, rs1799796), and XRCC7 Intron 8 (G6721T, rs7003908) by polymerase chain reaction-restriction fragment-length polymorphism methods. Variant genotype GG (odds ratio [OR], 2.23; p=0.003) and combined genotype TG+GG (OR, 1.541; p=0.049), G allele of XRCC7 Intron 8 (G>T), demonstrated significant risk for PCa (OR, 1.529; p=0.002). Stratification on bases of Gleason grade and bone metastasis, significant risk with high Gleason grade for CT genotype of XRCC3 Exon 7, and variant genotype GG of XRCC7 Intron 8 were observed. Our results strongly support that common sequence variants (GG) genotype of XRCC7 may increase risk of PCa. G allele being a risk allele in our study also suggests that this polymorphism be used as a marker for the PCa susceptibility.

Phylogeography and conservation of the endemic Hispaniolan Palm-Tanagers (Aves: Phaenicophilus)

The Gray-crowned Palm-Tanager (Phaenicophilus poliocephalus), sometimes considered conspecific with its more widespread congener P. palmarum, is restricted to Haiti’s Tiburon Peninsula, a biodiversity hotspot threatened by extensive habitat loss. We used a multilocus phylogeographic approach to identify evolutionarily distinct populations of Phaenicophilus. Mitochondrial haplotypes formed two reciprocally monophyletic groups separated by 5% uncorrected divergence. Genealogical patterns of differentiation at nuclear intron alleles were congruent with those of mtDNA, and the two species also differed in body size and shape. An ancient sea channel between the Tiburon Peninsula and mainland Haiti was likely a dispersal barrier that led to allopatric divergence, a hypothesis supported by our estimates of divergence times. Our results support the recognition of two Palm-Tanager species, confirming P. poliocephalus as Haiti’s only endemic bird species and underscoring the need to protect the Tiburon Peninsula’s single primary forest reserve.

Relationship between peroxisome proliferator-activated receptor alpha intron 1A/C genetic polymorphism and metabolic syndrome

To identify the relationship between genetic polymorphisms of peroxisome proliferator-activated receptor alpha (PPARalpha) intron 1A/C and metabolic syndrome (MS) in a Chinese population. A population-based case-control study was conducted in Suzhou city, Changshu County and Ganyu County in Jiangsu Province China, on the basis of an ongoing cohort study and 2348 cases were investigated. After the exclusion of the known MS cases, 1847 eligible subjects were successfully followed-up and their waist circumference (WC), body mass index, blood pressure, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fasting plasma glucose were measured. Newly diagnosed MS patients were recruited as cases, controls were individual matched with each case. TaqMan fluorescence probe method was used to detect the genetic polymorphism of PPARalpha intron 1A/C. The current analysis consisted of 389 MS patients and 389 matched controls. The C allele gene frequency of PPARalpha intron 1A/C in the case group was 22.24% (173/778), lower than that in the control group, which was 24.68% (192/778); whereas the difference was not statistically significant (chi(2) = 1.29, P > 0.05). In the genotypes AA + AC and CC, MS patients were accounted for 50.70% (363/716) and 41.94% (26/62) and hyperglycemia accounted for 21.37% (153/716) and 11.29% (7/62). Compared to the genotypes AA + AC, genotype CC was observed to be inversely associated with hyperglycemia (the adjusted OR = 0.39; 95%CI: 0.17 - 0.90) but not related to the occurrence of MS (OR = 0.75; 95%CI: 0.44 - 1.28) and other components of MS e.g., abdominal obesity (the adjusted OR = 0.67; 95%CI: 0.38 - 1.17), hypertriglyceridemia (the adjusted OR = 0.97; 95%CI: 0.53 - 1.76), low HDL-C (the adjusted OR = 0.72; 95%CI: 0.41 - 1.25) and hypertension (the adjusted OR = 0.72; 95%CI: 0.42 - 1.25) all P values > 0.05. C allele of PPARalpha intron 1A/C is not found to be associated with MS in the Chinese population. But comparing with the genotypes AA + AC, there is an inverse association between CC genotype and hyperglycemia.

Aquaporin-2 and -4: Single nucleotide polymorphisms in Ménière's disease patients

AbstractThe endolymphatic hydrops seen in Meniere's disease (MD) results from an inner ear fluid disequilibrium that has a suspected inherited component. Aquaporin-2 and aquaporin-4 (AQP2 and AQP4) water transport proteins may contribute to abnormal fluid homeostasis seen in MD. Our objective was to screen for sequence alterations in AQP2 and AQP4 genes in a northern European population with MD. Amplification for AQP2 (n = 18) and AQP4 (n = 30) was performed for patients with MD. Sequences were screened with denaturing high powered liquid chromatography (DHPLC) and confirmed with sequencing. Allele frequencies were compared with previously reported normal populations. We found that DHPLC failed to identify sequence alterations in any sample. Sequencing identified three intronic and one 3’ untranslated region polymorphism in AQP2, and one polymorphism upstream from the start codon in AQP4. Two of the AQP2 intronic allele frequencies showed an A and C allele enrichment, respectively, compared with a reporte...

Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study

BackgroundThe xenobiotic transporters, Multidrug Resistance 1 (MDR1/ABCB1) and Breast Cancer Resistance Protein (BCRP/ABCG2) may restrict intestinal absorption of various carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Cyclooxygenase-2 (COX-2) derived prostaglandins promote gastrointestinal carcinogenesis, affecting angiogenesis, apoptosis, and invasiveness.The aim of this study was to investigate if polymorphisms in these genes were associated with risk of colorectal cancer (CRC), and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use.MethodsThe following polymorphisms were analyzed; a synonymous MDR1 C3435T (rs1045642) in exon26, G-rs3789243-A in intron3, the functional BCRP C421A (rs2231142), the two COX-2 A-1195G (rs689466) and G-765C (rs20417) in the promoter region, and the COX-2 T8473C (rs5275) polymorphisms in the 3'-untranslated region. The polymorphisms were assessed together with lifestyle factors in a nested case-cohort study of 359 cases and a random cohort sample of 765 participants from the Danish prospective Diet, Cancer and Health study.ResultsCarriers of the variant allele of MDR1 intron 3 polymorphism were at 1.52-fold higher risk of CRC than homozygous wild type allele carriers (Incidence rate ratio (IRR) = 1.52, 95% Confidence Interval (CI): 1.12-2.06). Carriers of the variant allele of MDR1 C3435T exon 26 had a lower risk of CRC than homozygous C-allele carriers (IRR = 0.71 (CI:0.50-1.00)). There was interaction between these MDR1 polymorphisms and intake of red and processed meat in relation to CRC risk. Homozygous MDR1 C3435T C-allele carriers were at 8% increased risk pr 25 gram meat per day (CI: 1.00-1.16) whereas variant allele carriers were not at increased risk (p for interaction = 0.02). COX-2 and BCRP polymorphisms were not associated with CRC risk. There was interaction between NSAID use and MDR1 C3435T and COX-2 T8473C (p-values for interaction 0.001 and 0.04, respectively).ConclusionTwo polymorphisms in MDR1 were associated with CRC risk and there was interaction between these polymorphisms and meat intake in relation to CRC risk. Our results suggest that MDR1 polymorphisms affect the relationship between meat and CRC risk.

The Transcription Factor TFAP2B Is Associated With Insulin Resistance and Adiposity in Healthy Adolescents

Insulin resistance and central adiposity are strong risk indicators for type 2 diabetes and coronary heart disease. An important role for adipose tissue in the etiology and progression of these conditions has recently become more evident. A transcription factor, TFAP2B, has been shown to participate in the regulation of adipocyte metabolism, by facilitating glucose uptake and lipid accumulation, while simultaneously reducing insulin sensitivity, and recently a direct function for TFAP2B as an inhibitor of adiponectin expression was observed. In this study, we have investigated how insulin resistance, plasma adiponectin, and central adiposity, in a normal population of adolescents, are affected by genetic variability in TFAP2B. Our results show that both insulin sensitivity, as measured from levels of fasting glucose and insulin, and central adiposity, estimated by subscapular skinfold thickness, were significantly associated to genetic variability in TFAP2B. This association was restricted to males only, where carriers of the 4-repeat allele of intron 2 had higher insulin sensitivity and lower subscapular skinfold thickness. Levels of adiponectin did not show any association to the TFAP2B polymorphism, but was negatively correlated to central adiposity in females. These results suggest that reduction of TFAP2B expression could have a protective effect against future risk of complications associated with decreased insulin sensitivity and central adiposity, such as type 2 diabetes and coronary heart disease.