International journal of molecular epidemiology and genetics最新文献

The incidence of Gastroesophageal reflux disease (GERD) has increased remarkably worldwide. This study focuses on the background features of these patients and evaluates the two GERD sub types; none erosive (NERD) and erosive (ERD). In a case-control study, patients with reflux symptoms who had obtained a total score of 8-18 of the GERD questionnaire were included. Control group consisted of their families with lower scores and no reflux presentations. All demographic features were recorded. Then upper GI endoscopy performed and the cases divided into two sub groups: NERD and ERD. In the next step, all demographic data analyzed for these two subgroups. The data were analyzed using the SPSS software version 21. A number of 210 subjects included in each group (210 patients with GERD and 210 control group) with normal statistical distribution of age and gender. There was a significant relationship between GERD and BMI (P=0.001), eating fatty foods (P=0.0001), lying after meal (P=0.0001), drinking beverages with meal (0.0001), eating spicy food (0.006) and NSAIDs use (P=0.0001). Then the cases divided into two subgroups; NERD (n=146) and ERD (n=64). There were a significant relationship with eating salty-smoky food (P=0.005) and eating spicy food (P=0.011). The difference of BMI between NERD and ERD was remarkable but was not statistically significant. Our results showed that obesity is an important risk factor for GERD. Other possible risk factors such as NSAIDs use and certain foods and wrong habits like lying after meal should be addressed in future longitudinal surveys.

We conducted a follow-up association study across extended candidate chromosomal regions for uterine leiomyoma (UL), or fibroids, to search for loci influencing the size of UL in 916 premenopausal North American women participants to the NIEHS uterine fibroid study. Proportional odds models with adjustments for confounders were fitted to evaluate the association of a final set of 2,484 single nucleotide polymorphisms (SNPs) with the size of uterine fibroids measured by transabdominal and transvaginal ultrasounds. SNP association with UL size was tested in a case-only design comparing three categories of tumor size (small, medium and large tumors) and in a design that included UL-free controls as the lowest category of a four-level ordinal outcome to account for misclassifications due to small, undetected tumors. In the case-only design, rs2285789 in SORCS2 (sortilin-related VPS10 domain containing receptor 2) was the sole variant that remained significant after correction for multiple testing (Bonferroni-adjusted P=0.037). Several other SNPs, namely those located in MYT1L, TMCC1 and BRCA1, reached promising associations. In the design that included the controls, several genes of potential relevance to UL pathogenesis were associated (Bonferroni-unadjusted P < 0.01) with tumor size, particularly LIFR-AS1 (leukemia inhibitory factor receptor alpha-antisense RNA 1), which showed the strongest association (Bonferroni-unadjusted P=0.0006) among the genes with regulated expression in UL. In conclusion, SORCS2, a known GWAS candidate for circulating IGF-I and IGFBP-3, may act through IGF-I signaling to affect the size of fibroids. Through down-regulation of LIFR, LIFR-AS1 may mediate the inhibitory action of LIF (leukemia inhibitory factor), a cytokine involved in embryonic uterine development. Replication analyses are needed to substantiate our reported associations of SORCS2 and LIFR-AS1 with the size of fibroids.

Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans.

Studies on sirtuins (SIRT), a family of proteins with deacetylase activity, have provided convergent evidence of the key role of these enzymes in aging-linked physiological functions. The link between SIRT1 and longevity has emerged in model organism but few data are available in humans, in particular relying on longitudinal studies. Here, we assessed whether a genetic variant within SIRT1 gene promoter (rs12778366) was associated to human longevity. We analyzed 586 genomic DNA (gDNA) collected in the study "Treviso Longeva" (TRELONG), including elderly over 70 years of age from the municipality of Treviso, a town in the Northeast of Italy, with a 11-year follow-up. We genotyped SIRT1 rs12778366 by real-time polymerase chain reaction (RT-PCR) allelic discrimination assay. A cross-sectional analysis performed by comparing people over and under 85 years of age did not evidence association between rs12778366 and longevity. When we performed a longitudinal analysis considering mortality as dependent variable, we did not observe an association of rs12778366 with longevity in the whole population (corrected P-value = 0.33). However, when we stratified the TRELONG subjects according to circulating level of interleukin-6 (IL-6), a predictor of disability and mortality, we found that rs12778366 (TC+CC) carriers were at increased risk of mortality in comparison to the TT reference group (corrected P-value = 0.03, HR 1.47). Our data do not support a major role of rs12778366 in human longevity, but the stratified analysis on IL-6 suggests that this variant may be involved in the detrimental effect of high circulating IL-6 in the elderly.

Burkholderia pseudomallei is a soil dwelling Gram-negative bacteria predominates in Southeast Asia zone and the tropical part of Australia. Genetic diversity has been explored among various populations and environments worldwide. To date, little data is available on MLST profiling of clinical B. pseudomallei isolates in peninsular Malaysia. In this brief report, thirteen culture positive B. pseudomallei cases collected from a single population of Terengganu state in the Western Peninsular Malaysia and were confirmed by In-house TTS1-PCR. Isolates were subjected for multi-locus sequence typing (MLST) to explore their genotypic diversity and to investigate for possible clonal clustering of a certain sequence type. Patient's clinical information was examined to investigate for clinical correlation among the different genotypes. In spite of small sample set, MLST results indicated predictive results; considerable genotypic diversity, predominance and novelty among B. pseudomallei collected over a single geographically-located population in Malaysia. Massive genotypic heterogeneity was observed; 8 different sequence types with predominance of sequence type 54 and discovery of two novel sequence types. However, no clear pathogenomic or organ tropism clonal relationships were predicted.

Background: Autosomal forms of Alport syndrome represent 20% of all patients (15% recessive and 5% dominant). They are caused by mutations in the COL4A3 and COL4A4 genes, which encode a-3 and a-4 collagen IV chains of the glomerular basement membrane, cochlea and eye. Thin basement membrane nephropathy may affect up to 1% of the population. The pattern of inheritance in the 40% of cases is the same as autosomal dominant Alport syndrome: heterozygous mutations in these genes. The aim of this study is to detect new pathogenic mutations in the COL4A4 gene in the patients previously diagnosed with autosomal Alport syndrome and thin basement membrane nephropathy in our hospital.

Methods: We conducted a clinical and genetic study in eleven patients belonging to six unrelated families with aforementioned clinical symptoms and a negative study of COL4A3 gene. The molecular study was made by conformation of sensitive gel electrophoresis (CSGE) and direct sequencing of the fragments that show an altered electrophoretic migration pattern.

Results: We found two pathogenic mutations, not yet described: IVS3 + 1G > C is a replacement of Guanine to Cytosine in position +1 of intron 3, in the splicing region, which leads to a pathogenic mutation. c.4267C > T; p.P1423S is a missense mutation, also considered pathogenic. We also found seven new polymorphisms.

Conclusions: We describe two new pathogenic mutations, responsible for autosomal dominant Alport syndrome. The other families of the study were undiagnosed owing to problems in the method employed and the possibility of mutations in other genes, giving rise to other diseases with similar symptoms.

Background & aim: Hearing loss is the most frequent form of neurosensory deficit in humans. Although the majority of hereditary hearing loss is due to nuclear gene mutations, it has become clear the significant contribution of mitochondrial genes. The first mitochondrial mutation shown to cause non-syndromic hearing loss in humans was the A1555G mutation in the small ribosomal RNA gene (12S rRNA). It has been detected in hundreds of families of different ethnic backgrounds, making it one of the prevalent genetic causes of hearing loss currently identified. However, there are major differences between ethnic groups regarding the frequency of this mutation. Few studies have been made in Arab countries, especially in Egypt. Here we report the prevalence of the mitochondrial mutation A1555G among patients with non-syndromic hearing loss (NSHL) and in healthy individuals with normal hearing in the Egyptian population.

Subjects & methods: The study was conducted on 97 patients with SNHL and 300 unrelated healthy Egyptian individuals, with normal hearing, as normal control subjects. Polymerase chain reaction followed by restriction enzyme digestion was used to screen the DNA samples of all subjects for the A1555G mutation.

Results: Participants included 97 cases with SNHL, 46 males and 51 females. Their ages ranged from 1 month to 65 years with the mean age 6.2 years (SD ± 8.2). Paternal consanguinity was reported in 46% (35/76) of the studied families. The A1555G mutation was found in one of the 97 patients (1.3%), while it has not been detected in the 300 control samples.

Conclusion: Our findings indicate that, even in absence of exposure to aminoglycosides, the mitochondrial A1555G mutation is one of the potential causes of non-syndromic SNHL in the Egyptian population.

Hemoglobinopathies, disorders of hemoglobin structure and production, are one of the most common monogenic disorders in humans. Glucose 6 phosphate dehydrogenase deficiency (G6PD) is an inherited enzymopathy resulting in increased oxygen stress susceptibility of red blood cells. The distributions of these genetic traits in populations living in tropical and subtropical regions where malaria has been or is still present are thought to result from survival advantage against severe life threatening malaria disease. 384 male Tanzanian volunteers residing in Dar es Salaam were typed for G6PD, sickle cell disease and α-thalassemia. The most prominent red blood cell polymorphism was heterozygous α(+)-thalassemia (37.8%), followed by the G6PD(A) deficiency (16.4%), heterozygous sickle cell trait (15.9%), G6PD(A-) deficiency (13.5%) and homozygous α(+)-thalassemia (5.2%). 35%, 45%, 17% and 3% of these volunteers were carriers of wild type gene loci, one, two or three of these hemoglobinopathies, respectively. We find that using a cut off value of 28.6 pg. for mean corpuscular hemoglobin (MCH), heterozygous α(+)-thalassemia can be predicted with a sensitivity of 84% and specificity of 72% in this male population. All subjects carrying homozygous α(+)-thalassemia were identified based on their MCH value < 28.6 pg.

Background: Obesity has been linked to high dietary intake and low physical activity. Studies showed that those factors were not only regulated by environment but also by genetic. However, the relationship is less been understood in obese children and adolescents.

Objective: The objective of this study was to examine the role of SNPs in GHSR rs292216 and rs509035 on dietary intake in obese female adolescents.

Methods: This is an observational study with cross sectional design. Respondents were obese female adolescents enrolled from obesity screening done in six junior high schools in Yogyakarta. Dietary intake was measured using 6 days 24 hours inconsecutive dietary recall. Genotyping of 2 SNPs from GHSR was done using FRLP-PCR.

Results: There were 78 obese female adolescents joined this study. We found that no significant association between SNPs GHSR and dietary intake (p < 0.05). In addition, a SNP-SNP interaction analysis shown there is no difference between combination of GHSR rs292216 and rs509035 on dietary intake (p < 0.05).

Conclusion: We concluded that SNPs on GHSR rs292216 and rs509035 were not related to dietary intake in Indonesian obese female adolescents. Further study is necessary to investigate the effect of those genes on dietary intake in the broader population.

The soluble receptor for advanced glycation end-products (sRAGE) is shown to mitigate pro-inflammatory effects triggered by ligation of RAGE with N(ε)-carboxymethyl-lysine (CML)-AGE or other ligands. We examined the associations among host, lifestyle, and genetic determinants of CML-AGE or sRAGE and risk of pancreatic cancer in the prospective ATBC Study. We obtained baseline exposure information, data on serological and genetic biomarkers from 141 patients with pancreatic cancer and 141 subcohort controls. Stepwise linear and logistic regression models were used for data analysis. Multiple linear regression analyses showed that CML-AGE concentrations were independently inversely correlated with the minor allele of rs640742 of DDOST, physical activity, alcohol consumption, diastolic blood pressure (BP), and positively correlated with heart rate, serum sRAGE and HDL concentrations (P < 0.05). sRAGE concentrations were independently inversely correlated with the 82Ser allele of rs2070600 of RAGE, age, body mass index, heart rate, and serum HDL; and positively correlated with serum CML-AGE, sucrose consumption, and diastolic BP (P < 0.05). The minor allele of rs1035786 of RAGE was associated with reduced risk of pancreatic cancer (any T compared with CC: multivariate OR = 0.61, 95% CI: 0.38-0.98). We identified host metabolic profile, lifestyle and genetic factors that explained approximately 50% of variability of CML-AGE or sRAGE in Finnish men smokers. The association between RAGE SNPs and pancreatic cancer risk warrants further investigation.