ASSOCIATION OF POLYMORPHISM - 13910 C>T AND LCT GENE EXPRESSION WITH SYMPTOMS CHARACTERISTIC FOR LACTOSE INTOLERANCE AND THE RISK OF INFLAMMATORY BOWEL DISEASE

Laktozna netoleranca je avtosomno recesivna metabolna lastnost, ki je značilna za okrog 75% odraslega svetovnega prebivalstva. Posamezniki z laktozno netoleranco imajo mutacijo -13910C>T v genu LCT, ki povzroči znižano aktivnost encima laktaze, kar onemogoča popolno razgradnjo laktoze na glukozo in galaktozo v tankem črevesu, to pa povzroči neprijetne simptome, predvsem drisko, napenjanje, vetrovi neprijetnega vonja, brbotanje in bolečina v trebuhu. Raziskava opravljena na finski populaciji, je pokazala 100% povezavo med mutiranim CC genotipom in klinično dokazano laktozno netoleranco. V raziskavi smo določili frekvenco mutacije v promotorskem delu gena LCT v slovenski populaciji. V raziskavo smo zajeli 607 naključnih posameznikov, pri katerih smo preverili pogostost posameznega genotipa polimorfizma -13910C>T v genu LCT. Nadalje smo pri naključno izbranih posameznikih s pomočjo anketnega vprašalnika, ki je zajemal 42 vprašanj, preverili prehranske navade. V raziskavi smo iskali povezavo med genotipom polimorfizma -13910C>T v genu LCT, za laktozno netoleranco, s simptomi in vnosom laktoze ter merili ekspresijo gena LCT. Delež oseb z genotipom CC je bil 36,5%, delež oseb z genotipom CT 46,6% ter genotipom TT 16,8%. Pri preiskovancih smo preverili tedenski vnos laktoze ter primerjali vnos laktoze z posameznimi genotipi ter s pojavljanjem simptomov. Preiskovanci z genotipom CC so imeli višji vnos laktoze, kot preiskovanci z genotipoma CT in TT. Med preiskovanci, pri katerih so se simptomi pojavili po zaužitju mleka in mlečnih izdelkov, je bil vnos laktoze nižji kot pri preiskovancih, pri katerih simptomi se ne pojavijo po zaužitju mleka in mlečnih izdelkov (p=0,035, OI=-150,8-7,273). Med preiskovanci, ki imajo simptome značilne za laktozno netoleranco, je vnos laktoze prav tako nižji kot pri preiskovancih, ki so mnenja, da se ti simptomi pojavijo po zaužitju mleka in mlečnih izdelkov (p=0,031, OI=-154,03 - -8,11). V raziskavi smo merili tudi ekspresijo gena LCT v skupini anketiranih preiskovancev. Ekspresija gena LCT je bila med preiskovanci s simptomi bistveno nižja (27,87), kot med preiskovanci, ki nimajo simptomov značilnih za laktozno netoleranco (37,25). Primerjava se je izkazala kot statistično signifikantna (p=0,046). Naša raziskava je ena izmed redkih raziskav, ki ob genotipizaciji preverjajo tudi prehrambene navade preiskovancev, zato bi bilo potrebno naše ugotovitve potrditi in nadgraditi še na večjem številu vzorcev, saj bi bili rezultati tako še bolj zanesljivi. Naše ugotovitve bi lahko pomembno prispevale k razumevanju vpliva vnosa laktoze na izražanje simptomov pri osebah z bolezenskim genotipom CC polimorfizma -13910C>T v genu LCT in v prihodnosti morda prispevale delček k boljšemu poznavanju laktozne netolerance in s tem zmanjšanju težav mnogim posameznikom, ki trpijo zaradi simptomov, ki jih bolezen laktozna netoleranca povzroča.Lactose intolerance is an inherited autosomal recessive metabolic characteristic that affects approximately 75% of the adult world population. Individuals with lactose intolerance have a mutation -13910C> T in the LCT gene, which causes reduced activity of the enzyme lactase, which prevents the complete degradation of lactose to glucose and galactose in the small intestine, which causes unpleasant symptoms, primarily diarrhea, bloating, flatulence odor and abdominal pain. Research carried out on a Finnish population showed a 100% link between the mutant CC genotype and clinically proven lactose intolerance. In this study we determined the frequency of mutations in the promoter of the LCT gene in the Slovenian population. In the survey we evaluated 607 randomly chosen healthy individuals in which we examined the frequency of individual lactase genotypes. Through the questionnaire, which included 42 questions, we checked the nutritional habits of randomly selected individuals. In this study we searched for a connection between the medical, CC, genotype for lactose intolerance and the symptoms and lactose intake. We also measured the LCT gene expression. The prevalence of the CC genotype was 36,5%, CT genotype 46,6% and the TT genotype 16,8%. We checked the weekly intake of lactose and compare the weekly intake of lactose with the genotypes and the occurrence of symptoms. Subjects with CC genotype had a higher intake of lactose, such as subjects with CT and TT genotypes. The lactose intake was among subjects with symptoms after ingestion of milk and dairy products lower, than in subjects whose symptoms do not occur after ingestion of milk and milk products (p = 0.035, OI =- 150.8-7.273). The lactose intake was also lower among subjects with symptoms of lactose intolerance, than in subjects who are of the opinion that the symptoms occur after ingestion of milk and milk products (p = 0.031, OI =- 154.03 - -8.11 ). In this study we also measured the LCT gene expresion. LCT gene expression was among the subject with symptoms significantly lower (27,87) than among subjects without symptoms characteristic for lactose intolerance (37,25). The comparision has proved to be statisticaly significant (p=0,046). Our study is one of the few studies that don’t examine only the genotyping, but also the dietary habits of the subjects. Further studies and a larger number of samples are needed to confirm and to build further our findings. Our findings could have important contributions to understanding the influence of lactose on the expression of symptoms in subjects with medical, CC, genotype and may contribute in the future a fraction to a better knowledge of the lactose intolerance, thereby reducing the problem to many individuals, who suffer from symptoms of the disease lactose intolerance