Utjecaj genomske heterozigotnosti na kompenzaciju akutnog psihološkog stresa [The effect of genome heterozygosity on compensation of acute psychological distress]

Zgaga, Lina (2011) Utjecaj genomske heterozigotnosti na kompenzaciju akutnog psihološkog stresa [The effect of genome heterozygosity on compensation of acute psychological distress]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Background. Many studies have shown correlation between heterozygosity and fitness; particularly when organism is exposed to stress or when environmental conditions are detrimental. ----- The aim of this study was to investigate if standardized multi-locus heterozygosity is associated to morning cortisol concentration in response to acute psychological distress. Additional aim of the study was to perform genome-wide association study (GWAS) of cortisol, in order to identify genetic factors that affect cortisol concentration. ----- Methods. Custom-made questionnaire was used to collect general and lifestyle information of 924 study participants from the island of Vis. GHQ-30 was used to assess participants’ psychological state. DNA was extracted from blood and all samples were genotyped with STR and SNP markers. Standardized multilocus heterozygosity was calculated from the proportion of heterozygous STR markers for each individual. ----- Results. Multivariate analysis has shown statistically significant association of age, BMI, education, psychological distress and heterozygosity to cortisol concentration. Standardized multilocus heterozygosity is inversely associated to morning cortisol concentration (p=0.005). Genome-wide association study of cortisol has revealed a suggestive association of rs1000772 to morning cortisol concentration (p<0.00001). Searching the Ensembl database revealed that this SNP marker is located on chromosome 3p25.3 near GHRL. Literature search revealed that this gene codes for hormone ghrelin that is involved in regulation of cortisol secretion. -----Conclusion. Individuals with lower standardized multi-locus heterozygosity exhibit greater deviation in cortisol concentration following acute psychological distress (higher values), while the deviation from the normal values is smaller in more heterozygous individuals. These results suggest the possibility that more heterozygous individuals have a better ability to compensate psychological distress and better ability to retain homeostasis; hence they may also exhibit better fitness. There is suggestive evidence that SNP rs1000772 affects GHRL gene expression and thereby affects cortisol concentration, but additional studies are required.

Abstract in Croatian

Uvod. Mnogobrojne su studije pokazale kako heterozigotnost povećava fitnes i to osobito kada je jedinka izložena stresu ili kada su okolišni uvjeti nepovoljni. ----- Cilj je ovog istraživanja utvrditi modificira li standardizirana multilokusna heterozigotnost porast jutarnjih vrijednosti kortizola do kojih dolazi u sklopu odgovora na akutno narušenje psihičkog zdravlja. Dodatni je cilj rada napraviti cjelogenomsku asocijacijsku studiju koncentracije kortizola kako bi se identificirali genetički čimbenici koji utječu na koncentraciju kortizola. ----- Metode. Upitnikom su prikupljeni opći podaci i informacije o stilu života za 924 ispitanika s otoka Visa, a upitnikom GHQ-30 ispitano je njihovo psihičko zdravlje. DNK je izolirana iz krvi te je napravljena genotipizacija STR i SNP biljezima. Standardizirana multilokusna heterozigotnost izračunata je iz udjela heterozigotnih STR biljega za svakog ispitanika. ----- Rezultati. Multivarijatnom analizom je pokazano da su dob, BMI, obrazovanje, akutno psihičko stanje i heterozigotnost (sMLH) statistički značajno povezani s koncentracijom kortizola. Viša standardizirana multilokusna heterozigotnost povezana je s nižom koncentracijom kortizola (p=0,005). Cjelogenomskom analizom nađena je sugestibilna povezanost polimorfizma rs1000772 i jutarnje koncentracije kortizola (p<0.00001). Pregledom baze podataka „Ensembl“ utvrđeno je da se spomenuti SNP nalazi na kromosomu 3p25.3, u blizini gena GHRL. Ovaj gen kodira hormon grelin za koji je pregledom literature nađeno da je uključen u regulaciju lučenja kortizola. ----- Zaključak. Nađeno je da osobe smanjene heterozigotnosti pokazuju veći otklon vrijednosti kortizola od normale (tj. veći porast), dok je poremećaj koncentracije kortizola kod osoba povećane heterozigotnosti manji. Ovi rezultati upućuju na mogućnost da osobe povećane heterozigotnosti imaju bolji kapacitet kompenzacije akutno narušenog psihičkog zdravlja i održanja homeostaze, te posljedično i bolji fitnes. Rezultati cjelogenomske asocijacijske studije sugeriraju da polimorfizam rs1000772 modificira ekspresiju gena za grelin te tako utječe na koncentraciju kortizola, no rezultate je potrebno potvrditi dodatnim istraživanjima.

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