The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes

As the KL-VS haplotype alters secretion and activity of KLOTHO and uric acid (UA) is associated with endothelial dysfunction and inflammation, their mutual links may contribute to microalbuminuria (MA) in patients with type 1 diabetes (T1D). Therefore, we hypothesize that KL-VS polymorphism could be associated with the prevalence of MA in T1D patients, and KL-VS polymorphism could modify physiological functions and pathogenic potential of UA. We have examined 350 patients with T1D. The analysis concerned KL-VS polymorphism along with the concentrations of serum inflammatory markers, indicators of renal function, blood pressure, and lipid profile. The incidence of KL-VS genotype was lower in a group with MA in comparison to patients without this condition. Moreover, KL-VS carriers had improved indicators of renal function, lower concentrations of pro-inflammatory cytokines, and higher levels of anti-inflammatory markers. Simultaneously, among KL-VS carriers serum UA was negatively correlated with HbA1c, albumin excretion rate, ACR, CRP, TNF-α, total cholesterol, LDL-C and triglycerides, and positively correlated with HDL-C. Moreover, among wild-type KLOTHO carriers serum, UA was in positive correlation with creatinine, blood pressure, IL-12 and MCP-1, and in negative correlation with IL-10 and eGFR. Findings of our study suggest that the functional KL-VS polymorphism is independently associated with MA and the KL-VS genotype protects from the development of MA, and KL-VS polymorphism may modify physiological functions and pathogenic potential of UA by altering the levels of HbA1c, inflammatory biomarkers, indicators of renal function, blood pressure, and lipid profile. Key messages • We analyzed the KL-VS polymorphism and the UA serum level in patients with T1D. • The KL-VS polymorphism is independently associated with microalbuminuria. • The KL-VS alleles protect from the development of microalbuminuria. • KL-VS polymorphism may modify physiological functions and pathogenic potential of uric acid.

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“…DNA was stored at − 20°C until the time of use. Characterization of KL-VS polymorphism was analyzed as previously described [23].…”

Section: Methodsmentioning

confidence: 99%

A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents

et al. 2020

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“…Klotho protein is a cofactor of FGF23 and is a necessary protein to affect FGF23 on the receptor [34]. It is a circulating hormone involved in insulin signalling, inflammation, and vascular homeostasis through its protective effects on the endothelium and antioxidant actions [35]. Klotho expression occurs in various tissues.…”

Section: Klotho As Fgf23 Cofactormentioning

confidence: 99%

“…functional variant of the Klotho gene protects against the development of retinopathy in patients with DM1 [35]. An interesting issue is the relationship between the concentration of these proteins and the frequency and type of complications in people with type 1 diabetes, as well as the duration of the disease and the development of insulin resistance.…”

Section: Prace Poglądowementioning

confidence: 99%

“…Białko Klotho jest kofaktorem FGF23 i niezbędnym białkiem do funkcjonowania całego kompleksu [34]. Jest hormonem krążącym we krwi, zaangażowanym w sygnalizację na szlaku insuliny, stan zapalny i homeostazę naczyniową poprzez ochronne działanie na śródbłonek i funkcje przeciwutleniające [35]. Ekspresja Klotho zachodzi w różnych tkankach.…”

Section: Streszczenieunclassified

“…Możliwe jest także, że syntetyzowane w trzustce białko Klotho pełni funkcję zupełnie inną od poznanej. Ostatnie badania donoszą, iż synteza w komórkach trzustki powoduje tłumienie apoptozy komórek beta u pacjentów chorujących na CT1 [57], a wyniki najnowszych badań sugerują, że funkcjonalny wariant genu Klotho chroni przed rozwojem retinopatii u pacjentów z CT1 [35]. Ciekawym zagadnieniem pozostaje związek stężenia tych białek z częstością oraz rodzajem powikłań u osób chorujących na CT1, a także z długością trwania choroby i rozwojem IR, szczególnie w kwestii białka Klotho identyfikowanego jako białko starzenia i długowieczności.…”

Section: Streszczenieunclassified

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Klotho protein function among patients with type 1 diabetes

Flotyńska

Uruska

Araszkiewicz

et al. 2018

Endokrynologia Polska

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The fibroblast growth factor 23 (FGF23) and Klotho system play a very important role in the regulation of the human body metabolism. On the one hand, they promote longevity, and on the other hand they promote insulin resistance. Nowadays, accelerated aging in diabetes as the main consequence of chronic complications of the disease is postulated. Signalling pathways induced by insulin, insulin-like growth factor (IGF-1), and their homologues play an important role in controlling the aging process. Because FGF23/Klotho system affects glucose metabolism and gene expression of antioxidant enzymes, changes in its concentration may be a marker of chronic complications of diabetes or a treatment option. Despite huge improvements in the treatment of diabetes, its chronic complications remain an important clinical problem. An interesting issue is the relationship between the concentration of FGF23/Klotho and management of the disease, duration, insulin resistance, and development of complications in type 1 diabetes. (Endokrynol Pol 2018; 69 (6): 696-704)

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Association of KLOTHO polymorphisms with clinical complications of sickle cell anemia

et al. 2021

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The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes

Abstract: In conclusion, the findings of our studies suggest that the functional KL-VS variant of the KLOTHO gene protects against the development of retinopathy in patients with T1D.

Cited by 17 publications

References 41 publications

A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents

A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents

Klotho protein function among patients with type 1 diabetes

Association of KLOTHO polymorphisms with clinical complications of sickle cell anemia

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