{"id":1133,"date":"2016-12-05T22:24:31","date_gmt":"2016-12-05T21:24:31","guid":{"rendered":"http:\/\/www.newslab.sk\/2016\/12\/05\/studium-spoluucasti-genetickych-faktorov-na-diabetickej-retinopatii\/"},"modified":"2017-10-03T14:58:31","modified_gmt":"2017-10-03T12:58:31","slug":"studying-the-contribution-of-genetic-factors-to-the-development-of-diabetic-retinopathy","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/studying-the-contribution-of-genetic-factors-to-the-development-of-diabetic-retinopathy\/","title":{"rendered":"Studying the contribution of genetic factors to the development of diabetic retinopathy"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf <\/span><\/strong>\r\n attachment at the end of the paper. <\/span><\/strong><\/pre>\n
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Jednou z\u00a0najz\u00e1va\u017enej\u0161\u00edch komplik\u00e1ci\u00ed cukrovky (diabetes mellitus, DM) je retinopatia (DR), ktor\u00e1 po 20 rokoch trvania cukrovky takmer u\u00a0100 % pacientov vedie k\u00a0\u00faplnej strate zraku. Napriek v\u00fdznamn\u00fdm vedeck\u00fdm pokrokom v\u00a0etiopatogen\u00e9ze DR, toto ochorenie je st\u00e1le hlavnou pr\u00ed\u010dinou slepoty a\u00a0zhor\u0161enia zrakovej ostrosti v\u00a0popul\u00e1cii produkt\u00edvneho veku.<\/p>\n
Presn\u00e1 patogen\u00e9za DR nie je zatia\u013e objasnen\u00e1 ale sa uva\u017euje o\u00a0nieko\u013ek\u00fdch rizikov\u00fdch faktoroch. Na prvom mieste sa spom\u00edna d\u013a\u017eka trvania cukrovky a jej zl\u00e1 kompenz\u00e1cia. Z \u010fal\u0161\u00edch vonkaj\u0161\u00edch faktorov, ktor\u00e9 m\u00f4\u017eu ovplyvni\u0165 vznik a \u010fal\u0161\u00ed priebeh diabetickej retinopatie s\u00fa zn\u00e1me faj\u010denie, konzum\u00e1cia alkoholu, vysok\u00fd krvn\u00fd tlak, poruchy v hladin\u00e1ch krvn\u00fdch tukov, hormon\u00e1lna antikoncepcia.<\/p>\n
V\u00a0ostatn\u00fdch rokoch nazhroma\u017eden\u00e9 v\u00fdsledky a\u00a0pozorovania ale poukazuj\u00fa na to, \u017ee na v\u00fdvine DR sa v\u00fdznamne podie\u013eaj\u00fa aj genetick\u00e9 faktory. Tie d\u00f4kazy poch\u00e1dzaj\u00fa z\u00a0r\u00f4znych zdrojov. Na prvom mieste treba spomen\u00fa\u0165, \u017ee napriek rovnak\u00e9mu priebehu DM a\u00a0jeho kompenz\u00e1cie u\u00a0\u010dasti pacientov sa vyvinie DR u\u00a0inej nie. Dokonca aj v\u00a0pr\u00edpade jedn\u00e9ho z\u00a0najuzn\u00e1vanej\u0161\u00edch rizikov\u00fdch faktorov DR, \u010d\u00edm je d\u013a\u017eka trvania DM sa pozorovali v\u00fdznamn\u00e9 rozdiely. Niektor\u00ed postihnut\u00ed ani po mnoh\u00fdch rokoch nekompenzovan\u00e9ho DM nemaj\u00fa DR, k\u00fdm u\u00a0in\u00fdch u\u017e po kr\u00e1tkej dobe kompenzovan\u00e9ho DM sa pr\u00edznaky objavia (Uthra et al. 2008, Sun et al. 2011). Jedin\u00fdm vysvetlen\u00edm tohto pozorovania je odli\u0161n\u00e9 genetick\u00e9 pozadie u\u00a0DM pacientov (Schwartz et al. 2012). Okrem tohto nepriameho d\u00f4kazu existuje aj cel\u00fd rad priamych d\u00f4kazov. Na prvom mieste treba spomen\u00fa\u0165 etnick\u00fa pr\u00edslu\u0161nos\u0165, resp. popula\u010dn\u00e9 rozdiely vo v\u00fdskyte DR u\u00a0DM pacientov. Napr. v\u00fdrazn\u00e9 rozdiely sa na\u0161li u\u00a0afro-ameri\u010danov a\u00a0Ameri\u010danov eur\u00f3pskeho p\u00f4vodu (rozdielne genetick\u00e9 pozadie). V\u00a0prospech genetick\u00fd faktorov hovor\u00ed aj rodinn\u00e1 agreg\u00e1cia DR v\u00a0diabetick\u00fdch rodin\u00e1ch, ke\u010f riziko u\u00a0pr\u00edbuzn\u00fdch DM pacientov s\u00a0DR sa na\u0161la 3 n\u00e1sobne vy\u0161\u0161ia incidencia DR v\u00a0porovnan\u00ed s\u00a0rodinami DM pacientov bez DR (The diabetes control and complications trial research group 1997) .\u00a0\u00a0 Aj konkordancia v\u00fdskytu DR vykazuje zv\u00fd\u0161en\u00fa hodnotu u\u00a0monozygotn\u00fdch dvoj\u010diat v\u00a0porovnan\u00ed s\u00a0dizygotn\u00fdmi. Najpresved\u010divej\u0161ie d\u00f4kazy v\u0161ak poch\u00e1dzaj\u00fa priamo z\u00a0genetick\u00fdch anal\u00fdz. Napr. v\u00e4zbov\u00e1 anal\u00fdza odhalila v\u00a0\u013eudskom gen\u00f3me nieko\u013eko lokusov, ktor\u00e9 vykazovali v\u00e4zbu s\u00a0DR, aj ke\u010f samotn\u00e9 g\u00e9ny zatia\u013e neboli identifikovan\u00e9. Ide o\u00a0nasledovn\u00e9 chromoz\u00f3my: 1q36, 3, 5, 6, 9, 15, 19 a\u00a020 (Imperatore et al. 1998, Hallmann et al. 2007, Looker et al. 2007, Schwartz et al. 2012). Tret\u00edm zdrojom d\u00f4kazov o\u00a0spolu\u00fa\u010dasti genetick\u00fdch faktorov na v\u00fdvine DR s\u00fa asocia\u010dn\u00e9 \u0161t\u00fadia, \u010di u\u017e celo gen\u00f3mov\u00e9 (Grassi et al. 2011) alebo s\u00a0variantmi kandid\u00e1tnych g\u00e9nov (Roy MS. et al.2009, Balasubbu et al. 2010). Celogen\u00f3mov\u00fdch asocia\u010dn\u00fdch \u0161t\u00fadi\u00ed bolo doteraz uskuto\u010dnen\u00fdch len nieko\u013eko. Jedna \u0161t\u00fadia na mexick\u00fdch Ameri\u010danov odhalila asoci\u00e1ciu s variantom\u00a0g\u00e9nu CAMK4 na 5. chromoz\u00f3me a\u00a0s\u00a0variantom g\u00e9nu FMN1 v\u00a0lokuse 15q13 (Fu et al. 2010). Po\u010detnej\u0161ie s\u00fa \u0161t\u00fadi\u00e1, ktor\u00e9 sledovali asoci\u00e1ciu s\u00a0variantmi tzv. kandid\u00e1tnych g\u00e9nov. Ako kandid\u00e1tne g\u00e9ny sa analyzovali predov\u0161etk\u00fdm g\u00e9ny biochemick\u00fdch dr\u00e1h ako je polyolov\u00e1 dr\u00e1ha, \u201eincreased advenced glycation end products formation\u201c (AGE) dr\u00e1ha, \u201eglucose- induced\u201c dr\u00e1hy, angiogen\u00e9za, ren\u00edn \u2013 angitens\u00ednov\u00e1 dr\u00e1ha, \u201etissue matrix remodeling\u201c, aktiv\u00e1cia proteinkin\u00e1zy C (PKC), tvorba reakt\u00edvnych kysl\u00edkov, vaskul\u00e1rna endoteli\u00e1lna dysfunkcia a \u201eincreased hexosamine flux\u201c dr\u00e1ha (Balasubbu et al. 2006, Uthra et al. 2008, Ng 2010, Kuo et al. 2014). Pacienti s diabetes mellitus 2. typu maj\u00fa vysok\u00fa variabilitu terapeutick\u00fdch odpoved\u00ed na lie\u010dbu or\u00e1lnymi antidiabetikami, preto medzi kandid\u00e1tne g\u00e9ny mo\u017eno zaradi\u0165 aj g\u00e9ny, ktor\u00e9 maj\u00fa vz\u0165ah k farmakokinetike aj k\u00a0farmakodynamike t\u00fdchto or\u00e1lnych antidiabet\u00edk (CYP2C9, KCNJ11, ABCC8, TCF7L2, OCT1, OCT2 a MATE1, ATM a\u00a0pod.)<\/em><\/p>\n
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Preh\u013ead nieko\u013ek\u00fdch doteraz najviac analyzovan\u00fdch g\u00e9nov:<\/strong><\/p>\n
ALR2: <\/em>Na\u0161la sa asoci\u00e1cie CA opakovanie v\u00a0tomto g\u00e9ne s\u00a0DR v\u00a0nieko\u013ek\u00fdch pupul\u00e1ci\u00e1ch ako je \u010c\u00edna (Li et al. 2002), Japonsko (Fujisawa et al. 1999), India (Kumaramanickavel et al. 2003), \u010cile (Olmos et al. 2000), a Braz\u00edlia (Richeti et al. 2012). Na druhej strane tak\u00e1to asoci\u00e1cia sa nena\u0161la v\u00a0korejskej popul\u00e1cii (Park et al. 2002) a\u00a0v\u00a0jednej popul\u00e1cii Braz\u00edlie (Santos etal. 2003).<\/p>\n
RAGE: <\/em>Polymorfizmus 374T\/A vyk\u00e1zal asoci\u00e1ciu DR vo \u0160v\u00e9dsku a\u00a0v\u00a0Indii. Dokonca polymorfizmus Gly82Ser sa uk\u00e1zal ako protekt\u00edvne vo vz\u0165ahu k\u00a0DR v\u00a0Indii (Ramprasad et al. 2007, Balasubbu et al. 2010, Schwartz et al. 2012). Tieto v\u00fdsledky v\u0161ak neboli replikovan\u00e9 v\u00a0popul\u00e1cii \u010c\u00edny. Takisto polymorfizmus 429T\/C nevyk\u00e1zal asoci\u00e1ciu s\u00a0DR v\u00a0\u010c\u00edne ani v\u00a0Slovinsku.<\/p>\n
ATR1: <\/em>Tento g\u00e9n sa nach\u00e1dza v\u00a0oblasti na 3. chromozome, ktor\u00e1 vykazovala v\u00e4zbu s\u00a0DR.\u00a0 Napriek tomu v\u00a0s\u00fabore 827 pacientov z\u00a0\u010c\u00edny polymorfizmy tohto g\u00e9nu nevykazovali asoci\u00e1ciu s\u00a0DR.<\/p>\n
ACE: <\/em>Inzer\u010dno\/dele\u010dn\u00fd polymorfizmus tohto g\u00e9nu bol asociovan\u00fd s\u00a0DR u\u00a0japonsk\u00fdch pacientov, pacientov z\u00a0Ir\u00e1nu a\u00a0polymorfizmu rs4343 u pacientov\u00a0z\u00a0\u010c\u00edny (Abhary et al. 2009). Na druhej strane tak\u00e1to asoci\u00e1cia sa nena\u0161la u\u00a0283 pacientov zo \u0160panielska.<\/p>\n
VEGF<\/em>: Polymorfizmy prom\u00f3torovej oblasti tohto g\u00e9nu vykazovali siln\u00fa asoci\u00e1ciu s\u00a0DR v\u00a0japonskej Nakamura et al. 2009), v kaukazoidn\u00fdch popul\u00e1ci\u00e1ch (Awata et al. 2002, Ray et al. 2004), ale aj v\u00a0indickej popul\u00e1cii (Balasubbu et al. 2006). V\u00fdsledky asocia\u010dn\u00fdch \u0161t\u00fadi\u00ed polymorfizmov tohto g\u00e9nu s\u00a0DB zosumarizovali v\u00a0meta anal\u00fdze Lu et al. 2012.<\/p>\n
GSTT1: <\/em>U\u00a0604 pacientov kaukazoidn\u00e9ho p\u00f4vodu del\u00e9cia tohto g\u00e9nu u\u00a0DM\u00a0 pacientov s\u00a0DR bola dvakr\u00e1t \u010dastej\u0161ia ako u\u00a0pacientov bez DR.<\/p>\n
SOD2: <\/em>V\u00a0jednej \u0161t\u00fadii sa uk\u00e1zalo, \u017ee polymorfizmus tohto g\u00e9nu m\u00e1 protekt\u00edvny \u00fa\u010dinok vo\u010di DR (Demiryurek et al. 2010).<\/p>\n
HFE: <\/em>Na\u0161la sa asoci\u00e1cia mut\u00e1cie C282Y tohto g\u00e9nu s\u00a0DR u\u00a0kaukazoidn\u00fdch DM2 pacientov.<\/p>\n
PON1: <\/em>\u00a0Variant L\/L tohto g\u00e9nu je silne asociovan\u00fd s\u00a0v\u00fdvinom DR v\u00a0japonskej popul\u00e1cii (Abhary et al. 2009).<\/p>\n
PAI-1: <\/em>Del\u00e9cia 4G v\u00a0prom\u00f3torovej oblasti tohto g\u00e9nu bola asociovan\u00e1 s\u00a0vy\u0161\u0161\u00edm rizikom DR u\u00a0indi\u00e1nov kme\u0148a Pima (Nagi et al. 1997).<\/p>\n
a3-AR: <\/em>Takisto u\u00a0indi\u00e1nov Pima genotypy Arg\/Arg a\u00a0Arg\/Trp boli signifikantnej\u0161ie asociovan\u00e9 s\u00a0DR ako genoty Trp\/Trp (Nagi et al. 1997).<\/p>\n
Z vy\u0161\u0161ie uveden\u00e9ho vypl\u00fdva, \u017ee na v\u00fdvin DR m\u00e1 vplyv \u0161irok\u00e1 \u0161k\u00e1la g\u00e9nov, pri\u010dom sa d\u00e1 o\u010dak\u00e1va\u0165, \u017ee vplyv jednotliv\u00fdch g\u00e9nov bude pomerne mal\u00fd. Preto s\u00fa v\u00fdsledky anal\u00fdz jednotliv\u00fdch g\u00e9nov separ\u00e1tne m\u00e1lo signifikantn\u00e9, ba v\u00a0niektor\u00fdch pr\u00edpadoch aj protichodn\u00e9.<\/p>\n
Je v\u0161eobecne zn\u00e1me, \u017ee oxidat\u00edvny stres je v\u00fdznamn\u00fdm rizikov\u00fdm faktorom makro-, ale aj mikrovaskul\u00e1rnych patol\u00f3gi\u00ed. Nadprodukcia reakt\u00edvnych kysl\u00edkov\u00fdch radik\u00e1lov v\u00a0mitochondri\u00e1ch m\u00f4\u017ee by\u0165 v\u00a0pozad\u00ed t\u00fdchto patol\u00f3gi\u00ed. DR je vlastne mikrovaskul\u00e1rnou komplik\u00e1ciou DM. Preto mtDNA sa pova\u017euje za kandid\u00e1ta geneticky podmienenej susceptibility DR. Bolo uskuto\u010dnen\u00fdch nieko\u013eko \u0161t\u00fadi\u00ed, ktor\u00e9 sledovali asoci\u00e1ciu mitochondri\u00e1lnych haplotypov s\u00a0priebehom a\u00a0z\u00e1va\u017enos\u0165ou DR. V\u00a0jednej \u0161t\u00fadii zo strednej Eur\u00f3py sa na\u0161la v\u00fdznamn\u00e1 asoci\u00e1cia haplotypu T s\u00a0DR u\u00a0pacientov s\u00a0DM2 (Kofler et al. 2009). V\u00a0inej \u0161t\u00fadii, uskuto\u010dnenej v\u00a0Taliansku, zase haplotyp H bol signifikantne asociovan\u00fd s\u00a0DR. O\u00a0popula\u010dne \u0161pecifickej asoci\u00e1cie mtDNA haploskup\u00edn s\u00a0komplik\u00e1ciami DM (teda aj DR) referuj\u00fa in\u00ed autori v\u00a03 popul\u00e1ci\u00e1ch \u017eidovsk\u00e9ho p\u00f4vodu.<\/p>\n
Z\u00a0vy\u0161\u0161ie uveden\u00e9ho vypl\u00fdva, \u017ee spolu\u00fa\u010das\u0165 genetick\u00fdch faktorov na v\u00fdvine a\u00a0z\u00e1va\u017enosti DR u\u00a0DM pacientov je nesporn\u00e1. V\u00fdsledky doteraj\u0161\u00edch \u0161t\u00fadi\u00ed v\u0161ak ukazuj\u00fa, \u017ee objasnenie a\u00a0pochopenie ich \u00falohy e\u0161te vy\u017eaduje mnoh\u00e9 \u010fal\u0161ie extenz\u00edvne \u0161t\u00fadi\u00e1. Cie\u013eom n\u00e1\u0161ho projektu je vytvori\u0165 materi\u00e1lnu, vedomostn\u00fa a\u00a0metodick\u00fa infra\u0161trukt\u00faru a tak\u00a0 prispie\u0165 k\u00a0rie\u0161eniu tejto problematiky, \u010di u\u017e identifik\u00e1ciou niektor\u00fdch genetick\u00fdch faktorov, ktor\u00e9 sa podie\u013eaj\u00fa na patogen\u00e9ze DR, alebo identifik\u00e1ciou genetick\u00fdch markerov, ktor\u00e9 by umo\u017enili vytypova\u0165 jedincov so zv\u00fd\u0161enou n\u00e1chylnos\u0165ou na DR e\u0161te v\u00a0predklinickom \u0161t\u00e1diu, aby sa u\u00a0nich mohli aplikova\u0165 efekt\u00edvne prevent\u00edvne z\u00e1kroky. Je toti\u017e jednozna\u010dne potvrden\u00e9, \u017ee \u010d\u00edm v\u00a0skor\u0161\u00edch \u0161t\u00e1di\u00e1ch v\u00fdvinu sa zachyt\u00ed DR, t\u00fdm s\u00fa prevent\u00edvne z\u00e1kroky efekt\u00edvnej\u0161ie a\u00a0v\u00a0kone\u010dnom d\u00f4sledku m\u00f4\u017eu zachr\u00e1ni\u0165 zrak DM pacienta.<\/strong><\/p>\n
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Po\u010fakovanie: T\u00e1to publik\u00e1cia je v\u00fdsledkom implement\u00e1cie projektu \u201eCentrum v\u00fdskumu z\u00e1va\u017en\u00fdch ochoren\u00ed a\u00a0ich komplik\u00e1ci\u00ed\u201c, ITMS 26240120038, podporovan\u00fdch programom \u201eResearch & Developmental Operational Programme, ERDF\u201c.<\/p>\n
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Literat\u00fara<\/strong><\/p>\n
    \n
  1. Abhary S, Hewitt AW, Burdon KP et al.: A\u00a0systematic meta-analysis of genetic associationstudies for diabetic retinopathy. Diabetes, 58(9):2137-2147, 2009.<\/li>\n
  2. Awata T, Inoue K, Kurihara S, et al.: A\u00a0common polymorphism in the 5-prime-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes, 51:1635-1639, 2002.<\/li>\n
  3. Balasubbu S, Rajendran A, Ramasamy K, et al.: Emerging patterns of possible potential candidate gene polymorphisms associated with diabetic retinopathy \u2013 a\u00a0review. Assian J. Exp. Sci., 20:15-28, 2006.<\/li>\n
  4. Balasubbu S, Sundaresan P, Rajendran A, et al.: Association analysis of nine candidate gene polymorphisms in Indian patients with type 2 diabetic retinopathy. BMC Medical Genetics, 11:158, 2010.<\/li>\n
  5. Demiryurek AT, Erbagci I, Oztuczu S\u00a0et al.: Lacko f association between the Thr431Asn and Arg83Lys polymorphisms of the ROCK2 gene and diabetic retinopathy. Curr. Eye. Res., 35(12)1128-1134, 2010.<\/li>\n
  6. Fu Y-P, Hallman DM, Gonzalez VH et al.: Identification of diabetic retinopathy genes through a\u00a0genome-wide asociation study among Mexican-Americans from Starr County Texas. J. Ophzhalmol., doi:10.1155\/2010\/861291, 2010.<\/li>\n
  7. Fujisawa T, Ikegami H, Kawaguchi Y et al.: Length rather than a\u00a0specific allele of dinucleotide repeat in the 5\u2019upstream region of the algose reductase gene is associated with diabetic retinopathy. Med., 16:1044-1047, 1999.<\/li>\n
  8. Grassi MA, Tikhomirov A, Ramalingam S, et al.: Genome-wide meta-analysis for svere diabetic retinopathy. Hum. Molec. Genet., 20(12):272-2481, 2011.<\/li>\n
  9. Hallman DM, Boerwinkle E, Gonzalez V het al.: A\u00a0genome-vide linkage scan for diabetic retinopathy susceptibility genes in Mexican Americans with type 2 diabetes from Starr County, Texas. Diabetes, 56(4):1167-1173, 2007.<\/li>\n
  10. Imperatore G, Hanson RL, Pettitt DJ et al.: Sib-pair linkage analysis for susceptibility gene for microvascular complications among Pima Indians with type 2 diabetes. Diabetes, 47(5):821-830, 1998.<\/li>\n
  11. Kofler B, Mueller EE, Eder W, et al.: Mitochondrial DNA haplogroup T is associated with coronary artery disease and diabetic retinopathy: a\u00a0case control study. BMC Medical Genetics, 10(35):1\u20137, 2009.<\/li>\n
  12. Kumaramannickavel G, Sripriya S, Ramprasad VL, et al.: Z-2 aldose reductase allele and diabetic retinopathy in India. Ophthalmic Genet., 24:41-48, 2003.<\/li>\n
  13. Kuo JZ, Wong TY, Rotter JI: Challenges in elucidating the genetics of diabetic retinopathy. JAMA Ophthalmology, 132(1):96-107, 2014.<\/li>\n
  14. Li Q, Xie P, Huang J et al.: Polymorphisms and functions of the aldose reductase gene 5\u2019regulatory region in Chinese patients with type 2 diabetes mellitus. Chin. Med. J. (Engl), 115(2):209-213, 2002.<\/li>\n
  15. Looker HC, Nelson RG, Chew E, et al.: Genome-wide linkage analysis to identify loci for diabetes retinopathy. Diabetes, 56(4):1160-1166, 2007.<\/li>\n
  16. Lu Y, Shi Y, Ge Y, et al.: Two polymorphisms (rs699947. Rs2010963) in the VEGF gene and diabetic retinopathy: An updated meta-analysis. Diabetes and Metabolism, S:3, 2012.<\/li>\n
  17. Nagi DK, McCormack LJ, Mohamed-Ali V\u00a0et al.:Dibetic retinopathy, promoter (4G\/5G) polymorphism of KAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes. Dibetes Care, 20(8)1304-1309, 1997.<\/li>\n
  18. Nakamura S, Iwasaki N, Funatsu H, et al.: Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy. Graefes Arch. Clin. Exp. Ophthalmol., 247:21-26, 2009.<\/li>\n
  19. Ng PK: Human genetics of diabetic retinopathy: Current perspectives. J. Ophthalmol., doi:10.1155\/2010\/172593, 2010.<\/li>\n
  20. Olmos P. Futers S, Acosta AM, et al.: (AC)23 (Z-2) polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics. Diabetes Res. Cli. Pract., 47:169-176, 2000.<\/li>\n
  21. Park HK, Ahn CW, Lee GT, et al.: (AC)(n) polymorphismm of sldose reductase gene and diabetic microvascular complications in type 2 diabetes mellitus. Diabetes Res. Clin. Pract., 55:151-157, 2002.<\/li>\n
  22. Ramprasad S, Radha V, Mathias RA et al.: Rage gene promoter polymorphisms and diabetic retinopathy in clinic-based population from Soth India. Eye, 21(3):395-401, 2007.<\/li>\n
  23. Ray D, Mishara M, Read Davies R et al.: Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Diabetes, 53:861-864, 2004.<\/li>\n
  24. Richeti F, Noronha RM, Waetge RT, et al.: Evaluation of AC(n) and C(-106)T polymorfhisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy. Mol. Vis., 13:740-7415, 2007.<\/li>\n
  25. Roy MS, Hallman M, Fu YP, et al.: Assessment of 193 candidate genes for retinopaty in African Americans with type 1 diabetes. Arch. Ophthalmol. 127(5):605-612), 2009.<\/li>\n
  26. Santos KG, Tschiedel B, Schneider J, et al.: Diabetic retinopathy in Euro-Brazilian type 2 diabetic patients: relationship with polymorphisms in the aldose reductase, the plasminogen activator inhibitor-1 and the methylentetrahydrofolate reductase gene. Diabetes Res. Clin. Pract., 61:133-136, 2003.<\/li>\n
  27. Schwartz SG, Brantley MA, Flynn HW: Genetics an diabetic retinopathy. Current Diabetes Reviews, 9:86-92, 2012.<\/li>\n
  28. Sun JK, Keenan HA, Cavallerano JD, et al.: Protection from retinopathy and other complications in patients with type 1 diabetes of extrema duration. Diabetes Care, 34(4):968-974, 2011.<\/li>\n
  29. The diabetes control and complications trial research group. Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. Diabetes, 31(1):1829-1839, 1997.<\/li>\n
  30. Uthra S, Raman R, Mukesh BN et al.: Genetics of diabetic retinopathy. Int. J. Hum. Genet., 8(1-2):155-159, 2008.<\/li>\n<\/ol>\n
     <\/p>\n
     <\/p>\n","protected":false},"excerpt":{"rendered":"
    *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.   Jednou z\u00a0najz\u00e1va\u017enej\u0161\u00edch komplik\u00e1ci\u00ed cukrovky (diabetes mellitus, DM) je retinopatia (DR), ktor\u00e1 po 20 rokoch trvania cukrovky takmer u\u00a0100 % pacientov vedie k\u00a0\u00faplnej strate zraku. Napriek v\u00fdznamn\u00fdm vedeck\u00fdm pokrokom v\u00a0etiopatogen\u00e9ze<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[290],"tags":[737,734,735,736,738],"class_list":["post-1133","post","type-post","status-publish","format-standard","hentry","category-genetics","tag-candidate-genes","tag-diabetes-mellitus","tag-diabetic-retinopathy","tag-genetic-factors","tag-whole-genome-analysis","typ_clanku-review-article"],"acf":{"abstrakt":"
    Retinopathy (DR) represents one of the most serious complications of diabetes (diabetes mellitus, DM. After 20 years of diabetes, DR leads to complete loss of vision in nearly 100% of patients. Despite significant scientific progress in etiopathogenesis of DR, the disease is still the leading cause of blindness and worsening of visual acuity in the working age population. Although the exact pathogenesis of DR has not been clarified yet, a large amount of evidence has been accumulated recently showing significant involvement of genetic factors in the development and severity of DR. The results of previous studies show that clarification and understanding of their role still requires many more extensive studies. The aim of our project is to establish a material, knowledge-based and methodological infrastructure thus contributing to solving this problem, whether via identification of certain genetic factors involved in the pathogenesis of DR or by specifying the genetic markers that would allow identification of DM patients with increased susceptibility to DR who are still at the pre-clinical stage, which would, in turn enable application of effective preventive interventions.<\/p>\n
     <\/p>\n
    Key words:<\/strong> diabetes mellitus, diabetic retinopathy, genetic factors, candidate genes, whole genome analysis<\/p>\n","casopis":[{"ID":1000,"post_author":"7","post_date":"2015-11-21 14:33:24","post_date_gmt":"2015-11-21 13:33:24","post_content":"
    GENETICS<\/strong><\/h4>\r\n
      \r\n \t
    • The laboratory age<\/li>\r\n \t
    • The Odyssey of DNA reading<\/li>\r\n \t
    • Comparative genomic hybridisation: a methodological introduction<\/li>\r\n \t
    • Next generation sequencing and its application in clinical genetics<\/li>\r\n<\/ul>\r\n
      <\/h4>\r\n
      BIOCHEMISTRY<\/strong><\/h4>\r\n
        \r\n \t
      • Determining of the trace elements in blood serum<\/li>\r\n \t
      • Determining of \u03b1-tocopherol (vitamin E) in serum by way of liquid chromatography with tandem mass spectrometry (LC\/MS\/MS)<\/li>\r\n \t
      • Analysis of urinary calculi and its path to Europe<\/li>\r\n<\/ul>\r\n \r\n
        IMMUNOLOGY <\/strong><\/h4>\r\n
          \r\n \t
        • New autoantibodies in diagnosis of autoimmunity myopathies<\/li>\r\n \t
        • Taking advantage of flow-based cytometry in determining prognostic markers<\/li>\r\n<\/ul>\r\nCD38 and ZAP-70 in patients with B-CLL\r\n\r\n \r\n
          CYTOLOGY AND PATHOLOGY <\/strong><\/h4>\r\n
            \r\n \t
          • Mucinous ovarian carcinoma \u2013 news in diagnosis from the pathologist\u2019s perspective<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-12015","to_ping":"","pinged":"","post_modified":"2017-08-16 21:43:10","post_modified_gmt":"2017-08-16 19:43:10","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-12015\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"21","upload_clanok":{"ID":1134,"id":1134,"title":"medirex_1_2015-kadasi","filename":"MEDIREX_1_2015-\u2013-Kadasi.pdf","filesize":124987,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2016\/12\/MEDIREX_1_2015-\u2013-Kadasi.pdf","link":"https:\/\/www.newslab.sk\/en\/studying-the-contribution-of-genetic-factors-to-the-development-of-diabetic-retinopathy\/medirex_1_2015-kadasi\/","alt":"","author":"7","description":"","caption":"","name":"medirex_1_2015-kadasi","status":"inherit","uploaded_to":1133,"date":"2016-12-05 21:22:01","modified":"2016-12-05 21:22:01","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1133","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1133"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1133\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1133"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1133"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1133"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}