PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical subphenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.761029, OR = 1.40 (95% CI = 1.25–1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67–0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG .20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.761025, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

Journal of the proceedings of the Legislative Council of the Territory of the United States of America, South of the River Ohio : begun and held at Knoxville, the 29th day of June, 1795.

Originally published: Knoxville : G. Roulstone, 1795.

Köhler's Medizinal-Pflanzen in naturgetreuen Abbildungen mit kurz erläuterndem Texte : Atlas zur Pharmacopoea germanica, austriaca, belgica, danica, helvetica, hungarica, rossica, suecica, Neerlandica, British pharmacopoeia, zum Codex medicamentarius, sowie zur Pharmacopoeia of the United States of America /

v.1

Köhler's Medizinal-Pflanzen in naturgetreuen Abbildungen mit kurz erläuterndem Texte : Atlas zur Pharmacopoea germanica, austriaca, belgica, danica, helvetica, hungarica, rossica, suecica, Neerlandica, British pharmacopoeia, zum Codex medicamentarius, sowie zur Pharmacopoeia of the United States of America /

v.2

Köhler's Medizinal-Pflanzen in naturgetreuen Abbildungen mit kurz erläuterndem Texte : Atlas zur Pharmacopoea germanica, austriaca, belgica, danica, helvetica, hungarica, rossica, suecica, Neerlandica, British pharmacopoeia, zum Codex medicamentarius, sowie zur Pharmacopoeia of the United States of America /

v.3

Köhler's Medizinal-Pflanzen in naturgetreuen Abbildungen mit kurz erläuterndem Texte : Atlas zur Pharmacopoea germanica, austriaca, belgica, danica, helvetica, hungarica, rossica, suecica, Neerlandica, British pharmacopoeia, zum Codex medicamentarius, sowie zur Pharmacopoeia of the United States of America /

v.4

Pictorial national records : embracing descriptions of European and Asiatic nations: a statistical view of the United States of America, and a history of the great rebellion /

Mode of access: Internet.

Ye Horseforde booke : Horsford-Hosford families in the United States of America /

Mode of access: Internet.

Pharmacopoeia of the United States of America, The United States pharmacopoeia.

Two conventions were held in 1830, both of which issued a revision of Pharmacoepeia.

Five years' residence in the Canadas : including a tour through part of the United States of America, in the year 1823 /

Printed by James Nichols, Warwick Square, London.

Digest of comments on the pharmacopœia of the United States of America (eighth decennial revision) and the national formulary (third edition) for the calendar year ending December 31, 1908 /

At head of t.p. -- Treasury Department, Public Health and Marine-Hospital Service of the United States.

Digest of comments on The Pharmacopoeia of the United States of America and the National formulary for the calendar year ending December 31 ...

Vols. for 1911-1922 issued by the U.S. Public Health Service.

Secret proceedings and debates of the convention assembled at Philadelphia, in the 1787, : for the purpose of forming the Constitution of the United States of America /

"Biographical sketch" [of Robert Yates]: p. [329]-335.

Potential mitigation of midwest grass-finished beef production emissions with soil carbon sequestration in the United States of America

Beef production can be environmentally detrimental due in large part to associated enteric methane (CH4) production, which contributes to climate change. However, beef production in well-managed grazing systems can aid in soil carbon sequestration (SCS), which is often ignored when assessing beef production impacts on climate change. To estimate the carbon footprint and climate change mitigation potential of upper Midwest grass-finished beef production systems, we conducted a partial life cycle assessment (LCA) comparing two grazing management strategies: 1) a non-irrigated, lightly-stocked (1.0 AU/ha), high-density (100,000 kg LW/ha) system (MOB) and 2) an irrigated, heavily-stocked (2.5 AU/ha), low-density (30,000 kg LW/ha) system (IRG). In each system, April-born steers were weaned in November, winter-backgrounded for 6 months and grazed until their endpoint the following November, with average slaughter age of 19 months and a 295 kg hot carcass weight. As the basis for the LCA, we used two years of data from Lake City Research Center, Lake City, MI. We included greenhouse gas (GHG) emissions associated with enteric CH4, soil N2O and CH4 fluxes, alfalfa and mineral supplementation, and farm energy use. We also generated results from the LCA using the enteric emissions equations of the Intergovernmental Panel on Climate Change (IPCC). We evaluated a range of potential rates of soil carbon (C) loss or gain of up to 3 Mg C ha-1 yr-1. Enteric CH4 had the largest impact on total emissions, but this varied by grazing system. Enteric CH4 composed 62 and 66% of emissions for IRG and MOB, respectively, on a land basis. Both MOB and IRG were net GHG sources when SCS was not considered. Our partial LCA indicated that when SCS potential was included, each grazing strategy could be an overall sink. Sensitivity analyses indicated that soil in the MOB and IRG systems would need to sequester 1 and 2 Mg C ha-1 yr-1 for a net zero GHG footprint, respectively. IPCC model estimates for enteric CH4 were similar to field estimates for the MOB system, but were higher for the IRG system, suggesting that 0.62 Mg C ha-1 yr-1 greater SCS would be needed to offset the animal emissions in this case.

Internationalization strategy of ABotoa/Skypro shoes to United States of America

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics