Editing Gout (section)

==Cause==
[[File:Tophaceous gout affecting the arms and hands Wellcome L0062959.jpg|thumb|right|250px|Arms and hands of a 50-year-old man, showing large [[Tophus|tophi]] of [[Uric acid#Gout|sodium urate]] affecting the elbow, knuckles, and finger joints.]]

The [[crystallization]] of [[uric acid]], often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of [[Uric acid#Gout|urate]], the salts of uric acid.<ref name="Dalbeth2016"/> Underexcretion of uric acid by the kidney is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%.<ref name=Lancet2010/> About 10% of people with [[hyperuricemia]] develop gout at some point in their lifetimes.<ref name="pmid18327257">{{cite journal |vauthors=Vitart V, Rudan I, Hayward C, etal |title=SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout |journal=Nat. Genet. |volume=40 |issue=4 |pages=437–442 |date=April 2008 |pmid=18327257 |doi=10.1038/ng.106 |s2cid=6720464 |url=http://idiprints.knjiznica.idi.hr/373/ |access-date=27 July 2022 |archive-date=27 July 2022 |archive-url=https://web.archive.org/web/20220727105749/http://idiprints.knjiznica.idi.hr/373/ |url-status=live }}</ref> The risk, however, varies depending on the degree of hyperuricemia. When levels are between 415 and 530&nbsp;μmol/L (7 and 8.9&nbsp;mg/dL), the risk is 0.5% per year, while in those with a level greater than 535&nbsp;μmol/L (9&nbsp;mg/dL), the risk is 4.5% per year.<ref name=Egg2007/>

===Lifestyle===
Dietary causes account for about 12% of gout,<ref name=Review08>{{cite journal |vauthors=Chen LX, Schumacher HR |title=Gout: an evidence-based review |journal=J Clin Rheumatol |volume=14 |issue=5 Suppl |pages=S55–S62 |date=October 2008 |pmid=18830092 |doi=10.1097/RHU.0b013e3181896921 |s2cid=6644013 }}</ref>  and include a strong association with the consumption of alcohol, sugar-sweetened beverages,<ref>{{cite journal |vauthors=Ebrahimpour-Koujan S, Saneei P, Larijani B, Esmaillzadeh A |title=Consumption of sugar sweetened beverages and dietary fructose in relation to risk of gout and hyperuricemia: a systematic review and meta-analysis |journal=Crit Rev Food Sci Nutr |volume=60 |issue=1 |pages=1–10 |date=2020 |pmid=30277800 |doi=10.1080/10408398.2018.1503155 |s2cid=52909165 }}</ref> meat, and seafood.<ref name="Neogi2016"/> The dietary mechanisms and nutritional basis involved in gout provide evidence for strategies of prevention and improvement of gout, and dietary modifications based on effective regulatory mechanisms may be a promising strategy to reduce the high prevalence of gout.<ref>{{Cite journal |last1=Zhang |first1=Yingling |last2=Chen |first2=Simin |last3=Yuan |first3=Man |last4=Xu |first4=Yu |last5=Xu |first5=Hongxi |date=2022-08-26 |title=Gout and Diet: A Comprehensive Review of Mechanisms and Management |journal=Nutrients |language=en |volume=14 |issue=17 |pages=3525 |doi=10.3390/nu14173525 |doi-access=free |pmid=36079783 |pmc=9459802 |issn=2072-6643 }}</ref> Among foods richest in [[purines]] yielding high amounts of uric acid are dried [[anchovy|anchovies]], shrimp, [[organ meat]], dried [[Edible mushroom|mushrooms]], [[Edible seaweed|seaweed]], and [[beer yeast]].<ref>{{cite journal |last1=Kaneko |first1=Kiyoko |last2=Aoyagi |first2=Yasuo |last3=Fukuuchi |first3=Tomoko |last4=Inazawa |first4=Katsunori |last5=Yamaoka |first5=Noriko |title=Total Purine and Purine Base Content of Common Foodstuffs for Facilitating Nutritional Therapy for Gout and Hyperuricemia |journal=Biological and Pharmaceutical Bulletin |date=2014 |volume=37 |issue=5 |pages=709–721 |doi=10.1248/bpb.b13-00967 |pmid=24553148 |doi-access=free }}</ref> Chicken and potatoes also appear related.<ref name=Maj2018>{{cite journal |last1=Major |first1=Tanya J |last2=Topless |first2=Ruth K |last3=Dalbeth |first3=Nicola|author3-link= Nicola Dalbeth |last4=Merriman |first4=Tony R |title=Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts |journal=BMJ |volume=363 |date=10 October 2018 |pages=k3951 |doi=10.1136/bmj.k3951|pmid=30305269 |pmc=6174725 }}</ref> Other triggers include [[physical trauma]] and surgery.<ref name=Lancet2010/>

Studies in the early 2000s found that other dietary factors are not relevant.<ref name=Epi2008/><ref name=Choi2004>{{cite journal |vauthors=Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G |title=Purine-rich foods, dairy and protein intake, and the risk of gout in men |journal=[[N. Engl. J. Med.]] |volume=350 |issue=11 |pages=1093–1103 |date=March 2004 |pmid=15014182 |doi=10.1056/NEJMoa035700 |doi-access=free }}</ref> Specifically, a diet with moderate purine-rich vegetables (e.g., [[beans]], [[peas]], [[lentils]], and [[spinach]]) is not associated with gout.<ref name=Singh2011>{{cite journal|last1=Singh|first1=JA|last2=Reddy|first2=SG|last3=Kundukulam|first3=J|title=Risk factors for gout and prevention: a systematic review of the literature|journal=[[Current Opinion in Rheumatology]]|date=March 2011|volume=23|issue=2|pages=192–202|pmid=21285714|doi=10.1097/BOR.0b013e3283438e13|pmc=4104583}}</ref> Neither is [[Protein toxicity|total dietary protein]].<ref name=Choi2004/><ref name=Singh2011/> Alcohol consumption is strongly associated with increased risk, with wine presenting somewhat less of a risk than beer or [[distilled spirit|spirits]].<ref name="Singh2011" /><ref>{{cite journal |last1=Roddy |first1=E. |last2=Mallen |first2=C. D. |last3=Doherty |first3=M. |title=Gout |journal=BMJ |date=1 October 2013 |volume=347 |issue=oct01 3 |pages=f5648 |doi=10.1136/bmj.f5648 |pmid=24473446 |s2cid=220212466 }}</ref> Eating skim milk powder enriched with glycomacropeptide (GMP) and G600 milk fat extract may reduce pain but may result in diarrhea and nausea.<ref>{{cite journal|last1=Moi|first1=John HY|last2=Sriranganathan|first2=Melonie K|last3=Edwards|first3=Christopher J|last4=Buchbinder|first4=Rachelle|date=31 May 2013|title=Lifestyle interventions for chronic gout|journal=Cochrane Database of Systematic Reviews|volume=2013 |issue=5|pages=CD010039|doi=10.1002/14651858.cd010039.pub2|pmid=23728699|pmc=6759140|issn=1465-1858}}</ref>

Physical fitness, healthy weight, low-fat dairy products, and to a lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout;<ref>{{cite journal |vauthors=Hak AE, Choi HK |title=Lifestyle and gout |journal=Curr Opin Rheumatol |volume=20 |issue=2 |pages=179–186 |date=March 2008 |pmid=18349748 |doi=10.1097/BOR.0b013e3282f524a2 |s2cid=205485689 }}</ref><ref>{{cite journal |author=Williams PT |title=Effects of diet, physical activity and performance, and body weight on incident gout in ostensibly healthy, vigorously active men |journal=[[Am. J. Clin. Nutr.]] |volume=87 |issue=5 |pages=1480–1487 |date=May 2008 |pmid=18469274 |pmc=4090353 |doi=10.1093/ajcn/87.5.1480 }}</ref><ref name=Life2010>{{cite journal |author=Choi HK |title=A prescription for lifestyle change in patients with hyperuricemia and gout |journal=Curr Opin Rheumatol |volume=22 |issue=2 |pages=165–172 |date=March 2010 |pmid=20035225 |doi=10.1097/BOR.0b013e328335ef38 |s2cid=19146212 }}</ref><ref>{{cite journal|last1=Park|first1=Kyu Yong|last2=Kim|first2=Hyun Jung|last3=Ahn|first3=Hyeong Sik|last4=Kim|first4=Sun Hee|last5=Park|first5=Eun Ji|last6=Yim|first6=Shin-Young|last7=Jun|first7=Jae-Bum|title=Effects of coffee consumption on serum uric acid: systematic review and meta-analysis|journal=Seminars in Arthritis and Rheumatism|date=April 2016|volume=45|issue=5|pages=580–586|doi=10.1016/j.semarthrit.2016.01.003|pmid=26905267}}</ref> however, taking vitamin C supplements does not appear to have a significant effect in people who already have established gout.<ref name="Dalbeth2016"/> Peanuts, brown bread, and fruit also appear protective.<ref name=Maj2018/> This is believed to be partly due to their effect in reducing [[insulin resistance]].<ref name=Life2010/>

Other than dietary and lifestyle choices, the recurrence of gout attacks is also linked to the weather. High ambient temperature and low relative humidity may increase the risk of a gout attack.<ref>{{cite journal |last1=Neogi |first1=Tuhina |last2=Chen |first2=Clara |last3=Niu |first3=Jingbo |last4=Chaisson |first4=Christine |last5=Hunter |first5=David J. |last6=Choi |first6=Hyon |last7=Zhang |first7=Yuqing |date=15 August 2014 |title=Relation of Temperature and Humidity to the Risk of Recurrent Gout Attacks |journal=American Journal of Epidemiology |volume=180 |issue=4 |pages=372–377 |doi=10.1093/aje/kwu147 |issn=0002-9262 |pmc=4184385 |pmid=24993733}}</ref>

===Genetics===
Gout is partly genetic, contributing to about 60% of [[Genetic variability|variability]] in uric acid level.<ref name=Lancet2010/> The ''[[SLC2A9]]'', ''[[SLC22A12]]'', and ''[[ABCG2]]'' genes have been found to be commonly associated with gout and variations in them can approximately double the risk.<ref>{{cite journal|last=Merriman|first=TR|author2=Dalbeth, N|author2-link= Nicola Dalbeth |title=The genetic basis of hyperuricaemia and gout|journal= Joint Bone Spine|year=2011|volume=78|issue=1|pages=35–40|pmid=20472486|doi=10.1016/j.jbspin.2010.02.027}}</ref><ref name="Reginato2012">{{cite journal |vauthors=Reginato AM, Mount DB, Yang I, Choi HK |title=The genetics of hyperuricaemia and gout |journal=Nature Reviews Rheumatology|year=2012 |pmid=22945592 |doi=10.1038/nrrheum.2012.144 |volume=8 |issue=10 |pages=610–621 |pmc=3645862 }}</ref> [[Loss-of-function mutation]]s in ''SLC2A9'' and ''SLC22A12'' causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion.<ref name=Reginato2012/> The rare genetic disorders [[Tamm-Horsfall protein|familial juvenile hyperuricemic nephropathy]], [[medullary cystic kidney disease]], [[PRPSAP1|phosphoribosylpyrophosphate synthetase]] superactivity and [[hypoxanthine-guanine phosphoribosyltransferase]] deficiency as seen in [[Lesch–Nyhan syndrome]], are complicated by gout.<ref name=Lancet2010/>

===Medical conditions===
Gout frequently occurs [[Comorbidity|in combination with other medical problems]]. [[Metabolic syndrome]], a combination of [[abdominal obesity]], [[hypertension]], [[insulin resistance]], and [[Dyslipidemia|abnormal lipid levels]], occurs in nearly 75% of cases.<ref name=PM2010/> Other conditions commonly complicated by gout include [[lead poisoning]], [[kidney failure]], [[hemolytic anemia]], [[psoriasis]], [[organ transplant|solid organ transplants]], and [[myeloproliferative disorders]] such as [[polycythemia]].<ref name=Lancet2010/><ref name="pmid16392875">{{cite journal |vauthors=Stamp L, Searle M, O'Donnell J, Chapman P |title=Gout in solid organ transplantation: a challenging clinical problem |journal=Drugs |volume=65 |issue=18 |pages=2593–2611 |year=2005 |pmid=16392875 |doi=10.2165/00003495-200565180-00004|s2cid=46979126 }}</ref> A [[body mass index]] greater than or equal to 35 increases male risk of gout threefold.<ref name=Epi2008/> Chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.<ref>{{cite journal |author=Loghman-Adham M |title=Renal effects of environmental and occupational lead exposure |journal=Environ. Health Perspect. |volume=105 |issue=9 |pages=928–938 |date=September 1997 |pmid=9300927 |pmc=1470371 |doi= 10.2307/3433873|jstor=3433873}}</ref>

===Medication===
[[Diuretic]]s have been associated with attacks of gout, but a low dose of [[hydrochlorothiazide]] does not seem to increase risk.<ref name=CFP09/> Other medications that increase the risk include [[Niacin (substance)|niacin]], [[aspirin]] (acetylsalicylic acid), [[ACE inhibitor]]s, [[angiotensin receptor blocker]]s, [[beta blocker]]s, [[ritonavir]], and [[pyrazinamide]].<ref name="Dalbeth2016"/><ref name=Nature2009/> The [[immunosuppressive drug]]s [[ciclosporin]] and [[tacrolimus]] are also associated with gout,<ref name=Lancet2010/> the former more so when used in combination with hydrochlorothiazide.<ref>{{cite book |editor1-first=Gary S. |editor1-last=Firestein |editor2-first=Ralph C. |editor2-last=Budd |editor3-first=Edward D. |editor3-last=Harris |editor4-first= Iain B. |editor4-last=McInnes |editor5-first=Shaun |editor5-last=Ruddy |editor6-first=John S. |editor6-last=Sergent |title=Kelley's Textbook of Rheumatology |edition=8th |year=2008 |publisher=Elsevier |isbn=978-1-4160-4842-8 |chapter=Chapter 87: Gout and Hyperuricemia}}</ref> Hyperuricemia may be induced by excessive use of Vitamin D supplements. Levels of serum uric acid have been positively associated with 25(OH) D. The incidence of hyperuricemia increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001).<ref>{{cite journal |last1=Chen |first1=Yingchao |date=2020 |title=Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study. |url=https://rdcu.be/cHtkQ |journal=BMC Endocr Disord |volume=20 |issue=79 |page=79 |doi=10.1186/s12902-020-00560-1 |pmid=32493273 |pmc=7268462 |access-date=21 June 2021 |doi-access=free |archive-date=10 July 2024 |archive-url=https://web.archive.org/web/20240710063618/https://www.biomedcentral.com/epdf/10.1186/s12902-020-00560-1?sharing_token=2cW1CJCCbuDOmSgFjaRPuG_BpE1tBhCbnbw3BuzI2RPh6v_muYveTL-poMvfpyCalHaXszrUOCBZ-NGpeESiL0L0YQKZPY0oqu5huqTmGuIDlN9g0iJL3O3BCtGRpPDqRBNWnHFNYtFJW0A94ysz7f5HqEtewOugX5HVi3vR3AE%3D |url-status=live }}</ref>