ERCC6 founder mutation identified in Finnish patients with COFS syndrome

Jaakkola E, Mustonen A, Olsen P, Miettinen S, Savuoja T, Raams A, Jaspers NGJ, Shao H, Wu BL, Ignatius J. ERCC6 founder mutation identified in Finnish patients with COFS syndrome. Cerebro‐oculo‐facio‐skeletal (COFS) syndrome is an autosomal recessive disorder characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. We report a large consanguineous pedigree from northern Finland with six individuals belonging into four different sibships and affected with typical COFS syndrome phenotype. Two deceased patients have been published previously in 1982 as the first cases exhibiting cerebral calcifications typical for this disorder. Two living and one of the deceased patients were all shown to possess a novel homozygous mutation in the ERCC6 [Cockayne syndrome B (CSB)] gene, thereby confirming the diagnosis on molecular genetic level even for the earlier published cases. Genealogical investigation showed a common ancestor living in a northeastern village in Finland in the 18th century for all six patients implying a founder effect.     

Cold and heat strain during cold-weather field training with nuclear, biological, and chemical protective clothing

The objective of this study was to quantify the thermal strain of soldiers wearing nuclear, biological, and chemical protective clothing during short-term field training in cold conditions. Eleven male subjects performed marching exercises at moderate and heavy activity levels for 60 minutes. Rectal temperature (Tre), skin temperatures, and heart rate were monitored. Ambient temperature (Ta) varied from -33 to 0 degrees C. Tre was affected by changes in metabolism, rather than in Ta. Tre increased above 38 degrees during heavy exercise even at -33 degrees C. The mean skin temperature decreased to tolerance level (25 degrees C) at Ta below -25 degrees C with moderate exercise. Finger temperature decreased below 15 degrees C (performance degradation) at Ta of -15 degrees C or cooler. The present results from the field confirm the previous results based on laboratory studies and show that risk of both heat and cold strain is evident, with cooling of extremities being most critical, while wearing nuclear, biological, and chemical protective clothing during cold-weather training.     

Common polymorphisms (single-nucleotide polymorphisms SNP+45 and SNP+276) of the adiponectin gene regulate serum adiponectin concentrations and blood pressure in young Finnish men

Epidemiologic studies have shown that serum level of adiponectin, a circulating protein secreted by adipocytes, predicts the risk of type 2 diabetes and cardiovascular events. Two single-nucleotide polymorphisms (SNPs) at the adiponectin locus (T45G or G276T) of the adiponectin gene (APM1) have been associated with insulin resistance, low serum adiponectin levels, and diabetes. In the present study, the association of these polymorphisms with serum adiponectin level and insulin resistance-associated risk factors was investigated. To this aim, SNP+45 and SNP+276 of APM1 were genotyped in 252 young Finnish men. Serum adiponectin level (p < 0.001) and diastolic blood pressure (p = 0.031) were significantly higher in subjects with the T276T genotype of APM1 compared to those with the G276T or G276G genotypes. Mean diastolic blood pressure among the T276T subjects was 80 mmHg and that in subjects with the G276G and G276T genotypes below 75 mmHg. An interaction between triglycerides, diastolic blood pressure, quantitative insulin sensitivity check index, and SNP276 with regard to serum adiponectin level was found. After adjustment for other covariates, the interaction between triglycerides and SNP276 remained statistically significant (p = 0.009). Among subjects with the T276T genotype, an increase in triglyceride level was associated with a decrease in adiponectin concentration. This result was not observed in other genotype groups. SNP+45 was not significantly related to serum adiponectin concentration, but high-density lipoprotein (HDL) cholesterol tended to be higher in subjects with the T45T genotype (p = 0.051) compared to subjects with the X45G genotype. In conclusion, the T276T genotype of the adiponectin gene was associated with elevated serum adiponectin level and diastolic blood pressure among young Finnish men.     

Paternal and maternal exposure to welding fumes and metal dusts or fumes and adverse pregnancy outcomes

Objective  We assessed whether paternal exposure prior to conception and maternal exposure during pregnancy to welding fumes (WF) and metal dusts or fumes (MD/F) independently and jointly increases the risk of preterm delivery, low birth weight, and small-for-gestational age. Methods  The study population was selected from The Finnish Prenatal Environment and Health Study of 2,568 newborns (response rate 94%) and included 1,670 women who worked during pregnancy of which 68 were exposed either to WF and/or MD/F. Results  The risk of SGA was related to maternal exposure to WF only (adjusted OR = 1.78; 95% CI 0.53–5.99), MD/F only (adjusted OR = 1.77; 95% CI 0.38–8.35) and both exposures (2.92; 1.26–6.78). The corresponding effect estimates for preterm delivery were 2.66 (0.32–22.08), 5.64 (1.14–27.81) and for birth weight below 3,000 g 3.79 (1.09–13.19), 1.85 (0.56–6.14) and 1.70 (0.70–4.15), respectively. There was some suggestive, inconsistent evidence that the risk of preterm delivery and SGA is related to paternal exposure to WF. Conclusions  The present results provide evidence that maternal exposure to WF or MD/F combination during pregnancy may reduce fetal growth and suggestive evidence that paternal exposure to WF may increase the risk of preterm delivery and small-for-gestational age. The small number of exposed women and the lack of data for exposure concentrations suggest the need for further study to verify our findings.     

Work as a physician and adverse pregnancy outcomes: a Finnish nationwide population-based registry study

Work as a physician may be related to several occupational hazards. Only few studies have investigated the relations between work as a physician and the risk of adverse pregnancy outcomes and the results have been inconsistent. We conducted a nationwide population-based study in Finland to assess whether work as a physician during pregnancy increases the risk of adverse pregnancy outcomes. We identified from the 1990 to 2006 Finnish Medical Birth Register data all singleton newborns of physicians (N = 7,642) and other upper white collar workers (N = 124,606; as the reference group) from a source population of 946,392 singleton newborns. In generalized estimating equations, work as a physician was not related to low birth weight (adjusted odds ratio (OR) 1.00, 95% confidence interval (CI 0.86–1.15), preterm delivery (1.00, 0.89–1.12), small-for-gestational age (1.04, 0.86–1.22), large-for-gestational age (1.00, 0.86–1.13), perinatal death (0.88, 0.49–1.27), and the female gender of the newborn (0.98, 0.94–1.03). The risk of high birth weight (4,000 g or more; 0.88, 0.84–0.93) and postterm delivery were lower (0.77, 0.65–0.89) among physicians than the reference group. The results indicate that Finnish female physicians have a similar risk of adverse pregnancy outcomes as women of similar socio-economic background.     

Late pregnancy blood pressure in nulliparas and subsequent abnormal glucose tolerance

A growing body of evidence indicates that pregnancy-induced hypertension can be associated with features of insulin resistance. However, the impact of lower than hypertension-levels of blood pressure in pregnancy on the subsequent risk of developing abnormal glucose tolerance (AGT), has not been examined. We investigated women born in the years 1933-1956 and living in the municipality of Savitaipale, Finland, in May 1996. Prevalence of AGT was assessed by using oral glucose tolerance tests (OGTT). A retrospective chart review was carried out with regard to 216 nulliparas to obtain late pregnancy blood pressures. Logistic regression analyses showed that, after adjusting for body mass index (BMI) and age at OGTT, as well as for the number of subsequent pregnancies and the use of antihypertensive medication for PIH, 1 mmHg increase in systolic and diastolic blood pressure at late pregnancy in nulliparas increased the probability for AGT later in life 1.04-fold (OR, 1.04; 95% confidence interval, 1.00-1.09) and 1.06-fold (OR, 1.06; 95% confidence interval, 1.02-1.11), respectively. The results of this study suggest that not only hypertension but also less elevated levels of blood pressure during late pregnancy in nulliparas may be used as a predictor of subsequent AGT.