| 1. |
- Prokopenko, Inga, et al.
(författare)
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Variants in MTNR1B influence fasting glucose levels
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 x 10(-50)) and reduced beta-cell function as measured by homeostasis model assessment (HOMA-B, P = 1.1 x 10(-15)). The same allele was associated with an increased risk of type 2 diabetes (odds ratio = 1.09 (1.05-1.12), per G allele P = 3.3 x 10(-7)) in a meta-analysis of 13 case-control studies totaling 18,236 cases and 64,453 controls. Our analyses also confirm previous associations of fasting glucose with variants at the G6PC2 (rs560887, P = 1.1 x 10(-57)) and GCK (rs4607517, P = 1.0 x 10(-25)) loci.
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| 2. |
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| 3. |
- Chen, Wei-Min, et al.
(författare)
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Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
- 2008
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; Jun 2, s. 2620-2628
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.
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| 4. |
- Orru, Hans, 1980-, et al.
(författare)
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Evolution of traffic flows and traffic induced air pollution due to structural changes and development during 1993-2006 in Tartu (Estonia)
- 2008
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Ingår i: Baltic journal of road and bridge engineering. - 1822-427X. ; 3:4, s. 206-212
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Tidskriftsartikel (refereegranskat)abstract
- Traffic is the main factor affecting air quality in most cities. After the Estonian re-independence in 1991, the increase of motorization has been fast and car usage has intensified. During the same period, the average age of cars has decreased and thanks to improvements in engine technology, the emissions per km have been reduced. The objective was to see how these factors have reflected in air quality. This paper also aim to present an analytical approach to estimate the air pollution levels in recent years, when air quality monitoring has not been conducted, and available traffic data are limited. Based on traffic counts in 25 points across the city the amounts of traffic were modelled for 680 street segments with CUBE software. As air quality is monitored irregularly in Tartu, dispersion modelling was used to estimate pollution levels. Annual concentrations of exhaust particles (PMexhaust), particulate matter (PM10) and nitrogen oxides (NOx) in 1993, 2000 and 2006 were calculated with AEROPOL software. The traffic increase in the city centre of Tartu was especially rapid in the 1990s. In recent years, it has slowed due to congestion. Overall, traffic levels have increased more than 3 times since 1993. In residential areas, the increase is still rapid – up to 6 times from 1993 to 2006. However, the changes in air quality are less dramatic. Increases from 1993 to 2000 were followed by stable or slightly increasing pollution levels in recent years, especially in case of PMexhaust. The study showed that 2 factors, namely, increase of traffic and improvement of vehicles, have been compensating each other in the dynamics of air pollution.
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| 5. |
- Orrú, Valeria, et al.
(författare)
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A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus
- 2009
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:3, s. 569-579
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Tidskriftsartikel (refereegranskat)abstract
- A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.
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