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- Jacobsson, Josefin, et al.
(författare)
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Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children
- 2012
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 36:1, s. 119-129
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men. Design: Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children. Results: Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95% confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95% CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95% CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95% CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95%CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95% CI:0.093-0.373, P=0.001) and 0.147 (95% CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038). Conclusion: Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity.
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- Karalexi, M. A., et al.
(författare)
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Maternal fetal loss history and increased acute leukemia subtype risk in subsequent offspring : a systematic review and meta-analysis
- 2017
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Ingår i: Cancer Causes and Control. - : SPRINGER. - 0957-5243 .- 1573-7225. ; 28:6, s. 599-624
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Forskningsöversikt (refereegranskat)abstract
- Purpose History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted. Methods Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken. Results Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60). Conclusions In this meta-analysis involving > 50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.
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- Sällman Almén, Markus, et al.
(författare)
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Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children.
- 2013
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37:3, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- Background:The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index.Methods:In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD).Results:The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012).Conclusions:This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.
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- Siahanidou, T, et al.
(författare)
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Disparities of infant and neonatal mortality trends in Greece during the years of economic crisis by ethnicity, place of residence and human development index: a nationwide population study
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:8, s. e025287-
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Tidskriftsartikel (refereegranskat)abstract
- To study trends of infant mortality rate (IMR) and neonatal mortality rate in Greece during the period 2004–2016 and explore the role of sociodemographic factors in the years of crisis.DesignNationwide individual data for live births and infant (0–11 months) deaths provided by the Hellenic Statistical Authority were examined using Poisson, joinpoint regression and interrupted time series (ITS) analyses.SettingGreece.ParticipantsAll infant deaths (n=4862) over the 13-year period, of which 87.2% were born to Greek mothers, and respective live births.Main outcome measuresEvolution of IMR (0–364 days), early (<7 days) neonatal mortality rate (ENMR), late (7–27 days) neonatal mortality rate (LNMR) and post neonatal (28–364 days) mortality rate (PNMR) trends, by maternal nationality, place of residence and Human Development Index (HDI).ResultsBy Poisson regression, overall, during the study period, among infants of Greek mothers, IMR and PNMR declined significantly (−0.9%; 95% CI −1.7% to −0.1% and −1.6%; −3.0% to −0.2% annually, respectively), although differentially by place of residence (IMRurban: −2.1%; −2.9% to −1.3%, IMRrural: +10.6%; 7.6% to 13.6%). By contrast, among infants of non-Greek mothers, the low starting IMR/ENMR/LNMR/PNMR increased significantly (max ENMR:+12.5%; 8.6% to 16.5%) leading to a non-significant time–trend pattern overall in Greece. The inverse associations of HDI with IMR, ENMR and PNMR were restricted to Greek mothers’ infants. Joinpoint regression analyses among Greek mothers’ infants indicated non-significant increasing trends of IMR and ENMR following the crisis (+9.3%, 2012–2016, p=0.07 and +10.2%, 2011–2016, p=0.06, respectively). By contrast, the high (+17.1%; 8.1% to 26.9%, p=0.002) IMR increases among non-Greek infants were restricted to 2004–2011 and equalised to those of Greek mothers’ infants thereafter. ITS analyses in preset years (2008, 2010, 2012) identified significantly increasing trends in IMR, LNMR and PNMR after 2012, and in ENMR after 2010, among Greek mothers’ infants.ConclusionsHDI and rural residence were significantly associated with IMR. The strongly decreasing IMR trends among Greek-mothers’ infants were stagnated after a lag time of ~4 years of crisis approximating the previously sharply increasing trends among non-Greeks.
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- Skalkidou, A, et al.
(författare)
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Birth size and neonatal levels of major components of the IGF system : implications for later risk of cancer.
- 2002
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Ingår i: Journal of Pediatric Endocrinology & Metabolism (JPEM). - 0334-018X .- 2191-0251. ; 15:9, s. 1479-86
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Tidskriftsartikel (refereegranskat)abstract
- Pre- and perinatal conditions and processes may affect the risk for some forms of cancer in later life, while the insulin-like growth factor (IGF) system may play a role in both early somatic growth and later carcinogenesis. Birth weight and length, and the variation of major components of the IGF system immediately after birth, were analyzed in relation to selected physiological and pathological variables. The study comprised 331 healthy full-term newborns from whom blood samples were taken during routine phlebotomy no later than the fifth day of life. Measurements of IGF-I, IGF-II and IGF-binding protein-3 concentrations were performed. Birth length and weight were measured and information on socio-economic and medical variables was recorded. The concentrations of all three proteins were lower when blood bilirubin levels were high, possibly as a result of compromised liver function and/or as a component of an activated acute phase reaction. Birth weight was significantly higher by about 46 g among children whose IGF-I was higher by one SD, while the associations of birth weight and length with other components of the IGF system were in the predicted directions, albeit only in trend. We conclude that in early life, growth is related to the IGF system, mostly IGF-I. The latter is lower in children with jaundice, possibly because of hepatic dysfunction and/or as part of an acute phase reaction. We speculate that elevations of IGF-I in early life might explain the increased risk of cancer in individuals born with a higher birth weight.
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- Thomopoulos, Thomas P, et al.
(författare)
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Prelabor cesarean delivery and early-onset acute childhood leukemia risk.
- 2016
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Ingår i: European Journal of Cancer Prevention. - 0959-8278 .- 1473-5709. ; 25:2, s. 155-161
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Tidskriftsartikel (refereegranskat)abstract
- The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (≤3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996-2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0-14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10-2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13-2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15-2.40 and ORprelaborCD=1.79, 95% CI: 1.21-2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor.
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