Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Variant confidence”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2002

Validation of a new fluorogenic real-time PCR assay for detection of CYP2C9 allelic variants and CYP2C9 allelic distribution in a German population.

AIMS: The aim was to develop a fast detection method for the polymorphic alleles related to impaired CYP2C9-mediated metabolism. METHODS: CYP2C9 genotypes were identified in 118 DNA samples using real-time PCR (LightCycler) followed by melting curve analysis. All samples were re-tested by validated PCR-RFLP methodology. RESULTS: The concordance between the two methods was 100% for two variant alleles. The frequencies of CYP2C9*1 (wild type), CYP2C9*2 and CYP2C9*3 (with 95% confidence intervals) were 0.81(0.05), 0.14(0.04) and 0.05(0.03), respectively, and are similar to those observed in other Caucasian populations. CONCLUSIONS: This assay is simple and rapid and may be used for CYP2C9-genotyping in a clinical setting.

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Prevalence of alleles associated with HIV resistance in Russia.

Genetic polymorphisms of CCR5, CCR2, and SDF1 genes have been associated with resistance during human immunodeficiency virus type 1 (HIV-1) infection and disease progression. In the present report, we studied the frequency and co-occurrence of CCR5Delta32, CCR5-59029A/G, CCR2-64I, and SDF1-3'A allelic variants among HIV-1-seronegative individuals (n = 171) in Moscow. Observed allelic frequencies were 0.0906 [95% confidence interval (CI), 0.06-0.1212] for CCR5Delta32, 0.4072 (95% CI, 0.3542-0.4602) for CCR5-59029G, 0.1061 (95% CI, 0.0728-0.1394) for CCR2-64I, and 0.2218 (95% CI 0.1715-0.2721) for SDF1-3'A. A significant linkage disequilibrium (p = 0.0034) between CCR2-64I and SDF1-3'A alleles was observed.

Chemokine CXCL12↗
PubMed2026

Long-read based detection of large copy number variants with potential functional significance using the ContextSV structural variant caller.

Long-read sequencing enables improved detection of structural variants (SVs) in the human genome due to its substantially increased read lengths. However, currently widely used long-read SV callers primarily rely on alignment-based evidence, limiting their ability to detect large and complex SVs and potentially missing disease-relevant events. To address these limitations, we developed ContextSV, a framework that integrates alignment evidence with copy number predictions derived from sequencing coverage and single-nucleotide variant allele frequencies to improve SV detection, particularly for large copy number variants (CNVs). We additionally developed ContextScore, a machine learning-based classification model to assign SV confidence scores based on genomic context features and integrated it within ContextSV. Through benchmarking analyses on both simulated and real datasets, we demonstrate that ContextSV improves detection of large CNVs and inversions that may be missed by existing long-read SV callers. We further illustrate its utility by identifying and experimentally validating multiple large SVs in the KOLF2.1J reference stem cell line that were not detected by other methods. Collectively, our results demonstrate that ContextSV serves as a valuable complement to existing long-read SV detection approaches by improving sensitivity for large and clinically relevant SVs.

Humans↗
PubMed2004

Polymorphisms in genes involved in homologous recombination repair interact to increase the risk of developing acute myeloid leukemia.

PURPOSE: Double-strand break repair via homologous recombination is essential in maintaining genetic integrity. RAD51 and XRCC3 are involved in the repair of DNA by this pathway, and polymorphisms have been identified in both the RAD51 (RAD51-G135C) and XRCC3 (XRCC3-Thr241Met) genes. The object of this study was to examine whether these polymorphisms may modulate susceptibility to the development of acute myeloid leukemia (AML), a disease that is characterized by genetic instability. EXPERIMENTAL DESIGN: We studied the distribution of polymorphisms in RAD51 and XRCC3 in 216 cases of de novo AML, 51 cases of therapy-related AML (t-AML), and 186 control subjects using PCR followed by restriction enzyme digestion. The polymorphic deletion of the detoxification gene glutathione S-transferase M1 (GSTM1) was also examined by PCR. RESULTS: The risk of the development of AML was found to be significantly increased when both variant RAD51-135C and XRCC3-241Met alleles are present [odds ratio (OR), 3.77; 95% confidence interval (CI), 1.39-10.24], whereas the risk of t-AML development is even higher (OR, 8.11; 95% CI, 2.22-29.68), presumably because of the large genotoxic insult these patients receive after their exposure to radiotherapy or chemotherapy. If we further divide the AML group into patients in which the burden of DNA damage is increased, because of the deletion of the GSTM1 gene, the risk of development of AML is further increased (OR, 15.26; 95% CI, 1.83-127.27). CONCLUSIONS: These results strongly suggest that DNA double-strand breaks and their repair are important in the pathogenesis of both de novo and t-AML.

Adolescent↗
PubMedDate not supplied

Association between orosomucoid types and cancer.

Orosomucoid (ORM) is a polymorphic acute-phase reactant with immunosuppressive properties. Previous investigations have suggested that ORM and other acute-phase reactants may act as blocking factors protecting tumor cells against immunological attack, thereby contributing to the 'immune escape' of the tumor. ORM types were studied by isoelectric focusing and immunoprinting in patients with carcinoma of the breast, lung, ovary and endometrium and in population controls. In accordance with a previous study, the frequencies of the ORM1*2 allele and the ORM1 2 phenotype were found to be significantly increased in patients with different types of carcinomas. The results suggest that the ORM1 2 variant may influence the progression of cancer by being more immunosuppressive than the ORM1 1 variant. The relative risk for carcinoma in patients with the ORM1 2 type was 1.56 (95% confidence interval:1.16-2.09).

Alleles↗
PubMed1994

The partition coefficient as a predictor of local anesthetic potency for spinal anesthesia: evaluation of five local anesthetics in a mouse model.

Local anesthetic partition coefficients correlate with drug potencies in vitro, but in vivo data have not always complimented in vitro results. Despite extensive studies on intrathecal anesthetic action, whether there is correlation between the partition coefficient and local anesthetic potency has not been addressed. Mice (n = 150) were randomly allocated into 15 groups. Intrathecal injections of etidocaine (E), tetracaine (T), bupivacaine (B), lidocaine (L), or procaine (P) were administered and analgetic effect was measured using tail-flick (TF) test. Concentration-response regressions were constructed for each drug; EC50 values were calculated and compared at 95% confidence intervals. The EC50 values between E (0.017%), T (0.019%), and B (0.012%) were not significantly variant. The EC50 of L (0.098%) and P (0.229%) were significantly different from each other and from E, T, and B. The EC50 values were converted to ED50 in nmols. Relative anesthetic potency, defined as the inverse value of ED50 of drug was 23:16:15:2.4:1 for B, E, T, L, and P, respectively. ED50 showed high correlation (R = 0.978) with partition coefficients of local anesthetics. This study implies that the partition coefficient is a predictor of intrathecal local anesthetic potency. We suggest that the mouse model is reliable for evaluation of intrathecal local anesthetic action.

Anesthesia, Spinal↗
PubMed1993

The diagnostic and prognostic value of immunophenotyping in acute leukemia.

Immunophenotyping with monoclonal antibodies to leucocyte differentiation antigens has an established diagnostic role in the laboratory investigation of acute leukemia. In the vast majority of cases, a hemopoietic lineage can be confidently assigned; namely, acute myeloid leukemia (AML), or the precursor-B and precursor-T variants of acute lymphoblastic leukemia (ALL). The areas of greatest practical importance are in morphologically difficult or undifferentiated cases, and in distinguishing between the major variants of precursor-B and T-ALL. Cases with aberrant patterns of marker expression (acute mixed lineage leukemia, lineage infidelity) are frequently encountered in both ALL and AML, and can lead to diagnostic confusion. However, correlation with morphology and other clinicopathologic features, and careful consideration of the weight of phenotyping evidence almost always allows the correct lineage to be identified. The prognostic value of phenotypic information in acute leukemia is generally limited. Recognition of the major variants of ALL is still of clinical importance, but the significance of myeloid antigen positivity in ALL is controversial, and may not have prognostic value. Patterns of myeloid antigen expression in AML have limited prognostic significance, while the relationship between lymphoid antigen expression and treatment response in AML remains highly controversial. Careful evaluation of the predictive power of immunophenotype in large controlled clinical trials in acute leukemia is still required.

Antibodies, Monoclonal↗
PubMed2002

Host genetic polymorphism analysis in cervical cancer.

BACKGROUND: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. METHODS: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. RESULTS: The tumor necrosis factor-alpha (TNFalpha) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFalpha -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3' untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. CONCLUSIONS: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFalpha single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.

Cation Transport Proteins↗
PubMed2003

[Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing].

OBJECTIVE: XPD polymorphisms at Asp312Asn and Lys751Gln sites have been shown to modulate DNA repair capacity. The authors therefore assessed the relationship between these XPD polymorphisms and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based, case-control study. METHODS: Genotypes were determined by PCR-restriction fragment length polymorphism approaches in 383 healthy controls, 351 patients with lung cancer, and 325 patients with esophageal squamous cell carcinoma (SCC). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. RESULTS: Individuals carrying at least one 312Asn variant allele (Asp/Asn and Asn/Asn genotypes) were at an increased risk for lung SCC as compared with those with the Asp/Asp genotype (OR 1.80; 95% CI: 1.10-2.93; adjusted for age, sex and smoking), but this increased risk was not observed among patients with adenocarcinoma of the lung (adjusted OR: 1.07; 95% CI: 0.55-2.08). Furthermore, stratified analysis indicated a multiplicative interaction between tobacco smoking and the variant XPD 312Asn and 751Gln alleles on risk of lung SCC. The ORs of lung SCC for the variant XPD 312Asn and 751Gln alleles with smoking>or=29 pack/year were 12.44 (95% CI: 4.97-31.17) and 10.74 (95% CI: 4.51-25.57), respectively. No significant association between the Asp312Asn or Lys751Gln polymorphism and the risk of esophageal cancer was found. CONCLUSION: The above findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung SCC but not lung adenocarcinoma or esophageal SCC in this Chinese population.

Adenocarcinoma↗
PubMed2004

Large-scale candidate gene study of leprosy susceptibility in the Karonga district of northern Malawi.

We present a large case-control candidate gene study of leprosy susceptibility. Thirty-eight polymorphic sites from 13 genes were investigated for their role in susceptibility to leprosy by comparing 270 cases with 452 controls in Karonga district, northern Malawi. Homozygotes for a silent T-->C change in codon 352 of the vitamin D receptor gene appeared to be at high risk (odds ratio [OR] = 4.3, 95% confidence interval [CI] = 1.6-11.4, P = 0.004), while homozygotes for the McCoy b blood group defining variant K1590E in exon 29 of the complement receptor 1 (formerly CD35) gene appeared to be protected (OR = 0.3, 95% CI = 0.1-0.8, P = 0.02). Borderline evidence for association with leprosy susceptibility was found for seven polymorphic sites in an additional six genes. Some of these apparent associations may be false-positive results from multiple comparisons, and several associations suggested by studies in other populations were not replicated here. These data provide evidence of inter-population heterogeneity in leprosy susceptibility.

Adolescent↗
PubMed1994

The benefit of early treatment with immunosuppressive agents in lupus nephritis.

OBJECTIVE: In a cohort of 87 patients with lupus nephritis, delay between the detection of the onset of renal disease and renal biopsy was a significant predictor at the time of a first renal biopsy for subsequent renal insufficiency (relative risk - 4.9; 95% confidence interval = 1.7 to 14.5; p < 0.001) and death due to lupus renal involvement (relative risk = 6.7; 95% confidence interval = 2.1 to 21.2; p < 0.001). We evaluated the role of lead time bias, 2 variants of prognostic selection bias (length biased sampling), and the benefit of early treatment as explanations for this effect. METHODS AND RESULTS: Evaluation using the time of renal onset rather than the time of renal biopsy for the analysis suggested that lead time bias was unlikely to be an explanation for the effect of duration on renal insufficiency or death due to renal involvement. Identical values of age, serum creatinine and 24 hour urinary protein excretion at renal onset for those with a long duration versus short duration prior to biopsy, suggested that differences in prognostic selection were unlikely to explain the observed results. A 2nd type of prognostic selection bias arising from the failure to include patients who did not undergo a renal biopsy was further assessed by statistical simulation. The results of this approach indicated that prognostic selection bias was not solely responsible for the significant associations. Because treatment with high dose prednisone and immunosuppressive drugs was not instituted until a renal biopsy had been performed, delay in instituting these therapies remained a possible explanation for the increased frequency of renal insufficiency and death due to renal involvement observed in those with longer delays before renal biopsy. In addition, there was significant deterioration in serum creatinine (median change 0.6 mg/dl) and 24 hour urinary protein excretion (median change 2.5 gm) over the period from renal onset to renal biopsy, and significantly higher scores for the activity, chronicity and tubulointerstitial indices on renal biopsy in those in whom therapy was delayed. CONCLUSION: Prompt therapy with prednisone and immunosuppressive agents in lupus nephritis has a beneficial effect on longterm prognosis.

Adult↗
PubMed1994

Contrasting the distribution of chloroplast DNA and allozyme polymorphism among local populations of Silene alba: implications for studies of gene flow in plants.

The distribution of chloroplast DNA (cp-DNA) length variants was analyzed within and among 10 local populations of Silene alba, a dioecious angiosperm. The populations displayed considerable allele frequency variation, resulting in an estimate of Wright's Fst of 0.67 over a 25 x 25 km portion of the species' range. By contrast, a concurrent analysis of the genetic structure of these same populations based on seven polymorphic allozyme loci yielded an estimate of Fst of 0.13. The two Fst estimates are significantly different from one another when their respective confidence limits are estimated by jackknifing. The results of a breeding study were consistent with maternal inheritance of the cpDNA variants. With maternal inheritance the genetic structure of the cpDNA should reflect seed movement, whereas the genetic structure of the nuclear-encoded allozyme loci should reflect the movement of both seeds and pollen. Comparison of the two markedly different Fst estimates in the context of recent models of the population genetics of organelles suggests that the movement of both seeds and pollen contributes significantly to gene flow.

Journal Article↗
PubMed2007

Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18.

BACKGROUND: Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated. METHODS: Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages. RESULTS: Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants. CONCLUSIONS: The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN.

Adolescent↗
PubMed2005

Association of breast cancer risk with a common functional polymorphism (Asp327Asn) in the sex hormone-binding globulin gene.

Sex hormones play a central role in the development of breast cancer. Sex hormone-binding globulin (SHBG) modulates the bioavailability of circulating sex hormones and regulates their signaling system in the breast tissue. We evaluated the association of a common functional polymorphism (Asp327Asn) in the SHBG gene with breast cancer risk in a population-based case-control study (1,106 cases and 1,180 controls) conducted in Shanghai, China. The variant Asn allele was associated with a reduced breast cancer risk in postmenopausal women [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.53-0.99], but not in premenopausal women (OR, 1.03; 95% CI, 0.82-1.27). The protective association was much stronger in postmenopausal women with a low body mass index (BMI; OR, 0.46; 95% CI, 0.29-0.75) or waist-to-hip ratio (OR, 0.51; 95% CI, 0.32-0.83) than those with a high BMI or waist-to-hip ratio (P for interaction < 0.05). Furthermore, the association was stronger for estrogen receptor-positive (OR, 0.64; 95% CI, 0.42-0.98) than for estrogen receptor-negative breast cancer (OR, 0.85; 95% CI, 0.50-1.45). Among postmenopausal controls, blood SHBG levels were 10% higher in carriers of the variant Asn allele than noncarriers (P = 0.06). Postmenopausal control women with the Asn allele and low BMI or waist-to-hip ratio had 20% higher SHBG levels (P < 0.05). This study suggests that the Asn allele in the SHBG gene may be related to a reduced risk of breast cancer among postmenopausal women by increasing their blood SHBG levels.

Adult↗
PubMed2026

Revealing the Association of LIG1 Genetic Variants With Pterygium Susceptibility and Demographic Characteristics in a Taiwanese Population.

BACKGROUND/AIM: Pterygium is a common ocular surface disorder associated with long-term ultraviolet exposure and/or oxidative DNA damage. Accumulated evidence suggests that defects in DNA repair pathways may contribute to pterygium risk. DNA ligase I (LIG1), a key enzyme involved in DNA replication and base excision repair, has been involved in the etiology of several human diseases, including cancers. However, its role in pterygium has never been examined before. This study aimed at exploring the association between the LIG1 genotypes and pterygium risk in a Taiwanese population. PATIENTS AND METHODS: The hospital-based case-control study was conducted including 165 patients with pterygium and 320 age- and sex-matched non-pterygium controls. LIG1 rs20579 genotypes were accessed utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Stratified analysis and the calculation of odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used for evaluating the associations between genotypes and pterygium risk. RESULTS: Individuals carrying the homozygous variant AA genotype exhibited a significantly elevated risk of pterygium compared with those carrying the GG genotype (OR=2.74, 95% CI=1.17-6.43, p=0.0305). Under the recessive model, the AA genotype conferred a 2.65-fold elevated risk (95% CI=1.14-6.18, p=0.0350). The variant A allele was also associated with increased susceptibility (OR=1.46, 95% CI=1.03-2.07, p=0.0413). Stratified analyses revealed significant associations specifically among individuals aged &#x2265;60 years (OR=5.64, 95% CI=1.67-19.04, p=0.0039) and males (OR=5.23, 95% CI=1.74-15.73, p=0.0034), but not those of younger ages or females. CONCLUSION: The LIG1 rs20579 genotype is significantly associated with pterygium susceptibility in Taiwanese individuals, particularly among elderly and male subjects. These findings support the involvement of impaired DNA repair machinery in pterygium pathogenesis and suggest that LIG1 rs20579 may serve as a novel genetic biomarker for risk assessment and early detection of pterygium.

Humans↗
PubMed2006

Immunoglobulin G antibodies to merozoite surface antigens are associated with recovery from chloroquine-resistant Plasmodium falciparum in Gambian children.

We examined the hypothesis that recovery from uncomplicated malaria in patients carrying drug-resistant Plasmodium falciparum is a measure of acquired functional immunity and may therefore be associated with humoral responses to candidate vaccine antigens. Gambian children with malaria were treated with chloroquine in 28-day trials, and recovery was defined primarily as the absence of severe clinical malaria at any time and absence of parasitemia with fever after 3 days. Plasma samples from these children were assayed by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) to recombinant merozoite antigens: apical membrane antigen 1 (AMA-1) and the 19-kDa C-terminal region of merozoite surface protein 1 (MSP-1(19)), including antigenic variants of MSP-1(19) with double and triple substitutions. Antigen-specific IgG was more frequent in children who recovered, particularly that for MSP-1(19) (age-adjusted odds ratios: 0.32 [95% confidence interval, 0.05, 1.87; P = 0.168] for AMA-1, 0.19 [0.03, 1.11; P = 0.019] for recombinant MSP-1(19), 0.24 [0.04, 1.31; P = 0.032] for the recombinant MSP-1(19) double variant, and 0.18 [0.03, 0.97; P = 0.013] for the triple variant). IgG titers to MSP-1(19) and to the triple variant were higher in plasma samples taken 7 days after chloroquine treatment from children who carried resistant parasites but recovered and remained parasite free. Moreover, in children who were parasitemic on day 14 or day 28, there was an age-independent relationship between parasite density and IgG to both MSP-1(19) and the triple variant (coefficients of -0.550 and -0.590 and P values of 0.002 and 0.001, respectively). The results validate the use of this approach to identify antigens that are associated with protection from malaria.

Animals↗
PubMed1999

Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men.

AIMS/HYPOTHESIS: The objectives of the present investigation were to examine: 1) whether a Pro115Gln variant in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with juvenile-onset obesity among Danish Caucasianmen and 2) whether the relation of a Pro12Ala polymorphism in PPAR-gamma2 with BMI and long-term weight regulation differ between lean and obese subjects within the same cohort. METHODS: The Pro115Gln and Pro112Ala variants were examined using PCR and RFLP in a group of 752 subjects with a Body Mass Index (BMI) of 31.0 kg/m2 or more and in 869 non-obese control subjects. RESULTS: We did not find Pro115Gln in any of the 1621 male subjects we examined. Among the males with juvenile-onset obesity, the allelic frequency of the Pro12Ala polymorphism was 14% (95% confidence interval: 12-16%) compared with 16% (14-17%) among the non-obese control subjects (NS). Heterozygosity of the codon 12 variant was not associated with differences in BMI or changes in body weight regulation during follow up in lean or obese subjects. In the group of obese subjects, 21 homozygous Ala12Ala carriers had, however, a higher BMI (38.9 +/- 5.4 kg/m2 (means +/- SD) vs 35.5 +/- 5.5 kg/ m2, p = 0.008) and a higher weight gain (0.27 +/- 0.24 kg x m(-2) x year(-1) vs 0.10 +/- 0.24 kg x m(-2) x year(-1), p = 0.004), compared with wild-type carriers. Moreover, within the control group of 869 men the 14 homozygous carriers of the variant had a lower BMI (24.4 +/- 2.7 kg/m2 vs 26.2 +/- 3.7 kg/m2, p = 0.005) and a slower increase in BMI (0.11 +/- 0.11 kg x m(-2) x year(-1) vs 0.17 +/- 0.11 kg x m(-2) x year(-1), p = 0.002) compared with wild-type carriers. CONCLUSION/INTERPRETATION: The codon 12 variant of PPAR-gamma2 is not intrinsically associated with juvenile obesity. The variant may in its homozygous form interact, however, with various combinations of genetic and environmental factors in lean and obese subjects to cause divergent modulating effects on BMI and long-term body weight control.

Adult↗
PubMed2006

Reduced folate carrier gene G80A polymorphism is associated with an increased risk of gastroesophageal cancers in a Chinese population.

Low folate intake has been associated with an increased risk of both oesophageal and gastric cancers. Reduced folate carrier (RFC1, also named SLC19A1) is an essential folate transporter and functions as a bidirectional anion exchanger, taking up folate cofactors and exporting various organic anions. A G80A polymorphism in RFC1 gene has been shown to be associated with alterations in folate and homocysteine metabolism in healthy individuals. In this study, we hypothesised that genetic variants in RFC1 may modulate risk of oesophageal cancer (EC) and gastric cancer (GC). To test this hypothesis, we evaluated the associations of the G80A polymorphism of RFC1 with EC and GC risk in a case-control study of 216 EC and 633 GC cases and 673 cancer-free controls in a Chinese population. We found that compared with the 80GG/GA genotypes in the recessive model, the variant homozygote RFC1 80AA was associated with a significantly increased risk of EC (adjusted odds ratio (OR)=1.80, 95% confidence interval (CI)=1.29-2.51), GC (adjusted OR=1.59, 95% CI=1.25-2.02) and EC and GC combined (adjusted OR=1.63, 95% CI=1.30-2.04). In the dominant model, the risk associated with RFC1 80AA was also elevated in EC (OR=1.35, 95% CI=0.91-1.99), GC (OR=1.43, 95% CI=1.07-1.91) and EC and GC combined (adjusted OR=1.40, 95% CI=1.07-1.83), compared with the 80GG genotype. The stratification analyses showed that effects of the RFC1 80AA genotype were more evident in subgroups of relatively older (60 years), female, non-smokers, and non-drinkers both in EC and GC. Although the exact biological mechanism of this association remains to be explored, our findings suggest possible involvement of RFC1 variant in the susceptibility of EC and GC. Further large and functional studies are needed to confirm our findings.

Adult↗