A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P= 1.2 × 10−4). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7–2.3 for lung cancer(LC;P= 4.0 × 10−4), chronic obstructive pulmonary disease (COPD;P= 9.3 × 10−4), peripheral artery disease (PAD;P= 0.090) and abdominal aortic aneurysms (AAAs; P= 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49,P= 2.2 × 10−4), COPD (OR = 3.22,P= 2.9 × 10−4), PAD (OR = 3.47,P= 9.2 × 10−3) and AAA (OR = 6.44, P= 6.3 × 10−3). Joint analysis of the four smoking-related diseases reveals significant association (P= 6.8 × 10−5), particularly for early-onset cases (P=2.1 × 10−7). Our results are in agreement with functional studies showing that the human α4β2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation

Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of alpha-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of alpha-tocopherol, alcohol consumption, and age. Both the plasma concentration of alpha-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins

Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women

To access Publisher full text version of this article. Please click on the hyperlink in Additional LinkPUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of α-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of α-tocopherol, alcohol consumption, and age. Both the plasma concentration of α-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins

Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women

To access Publisher full text version of this article. Please click on the hyperlink in Additional LinkPUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of α-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of α-tocopherol, alcohol consumption, and age. Both the plasma concentration of α-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins

Positive association between plasma antioxidant capacity and n-3 PUFA in red blood cells from women.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPUFA are susceptible to oxidation. However, the chain-reaction of lipid peroxidation can be interrupted by antioxidants. Whether an increased concentration of PUFA in the body leads to decreased antioxidant capacity and/or increased consumption of antioxidants is not known. To elucidate the relationship between plasma total antioxidant capacity (TAC), the concentration of antioxidant vitamins, and the proportion of PUFA in red blood cells (RBC), plasma TAC was measured by a Trolox equivalent antioxidant capacity assay in blood samples from 99 Icelandic women. Concentrations of tocopherols and carotenoids in the plasma were determined by HPLC, and the FA composition of RBC total lipids was analyzed by GC. Plasma TAC and the plasma concentration of alpha-tocopherol correlated positively with the proportion of total n-3 PUFA, 20:5n-3, and 22:6n-3 in RBC, whereas the plasma lycopene concentration correlated negatively with the proportion of total n-3 PUFA and 20:5n-3. On the other hand, plasma TAC correlated negatively with the proportion of n-6 PUFA in RBC. Plasma TAC also correlated positively with the plasma concentration of alpha-tocopherol, alcohol consumption, and age. Both the plasma concentration of alpha-tocopherol and age correlated positively with the proportion of n-3 PUFA in RBC; however, n-3 PUFA contributed independently to the correlation with plasma TAC. Because the proportion of n-3 PUFA in RBC reflects the consumption of n-3 PUFA, these results suggest that dietary n-3 PUFA do not have adverse effects on plasma TAC or the plasma concentration of most antioxidant vitamins

Campylobacter spp. in Icelandic poultry operations and human disease.

We describe the observed relationship of campylobacter in poultry operations to human cases in a closed environment. During 1999 in Iceland, domestic cases of campylobacteriosis reached peak levels at 116/100,000 and in 2000 dropped to 33/100,000. Approximately 62% of broiler carcass rinses were contaminated with Campylobacter spp. in 1999. During 2000, only 15% of the broiler flocks tested Campylobacter spp. positive. In 2000, carcasses from flocks which tested positive on the farms at 4 weeks of age were subsequently frozen prior to distribution. We suggest that public education, enhanced on-farm biological security measures, carcass freezing and other unidentified factors, such as variations in weather, contributed to the large reduction in poultry-borne campylobacteriosis. There is no immediate basis for assigning credit to any specific intervention. We continue to seek additional information to understand the decline in campylobacteriosis and to create a risk assessment model for Campylobacter spp. transmission through this well defined system