Nejvíce citovaný článek - PubMed ID 21208019
The connexin 37 (1019C>T) gene polymorphism is associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with central obesity
BACKGROUND: The associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors. METHODS: In a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391). RESULTS: In 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol - LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene. CONCLUSION: In addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials.
- Klíčová slova
- Cardiovascular risk factors, Gene for connexin 37, Sex, Type 1 diabetes mellitus, Vascular parameters,
- MeSH
- diabetes mellitus 1. typu * genetika patofyziologie MeSH
- diabetické angiopatie genetika patofyziologie MeSH
- dospělí MeSH
- fenotyp MeSH
- fotopletysmografie MeSH
- genetická predispozice k nemoci MeSH
- hodnoty glomerulární filtrace MeSH
- intimomediální šíře tepenné stěny MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- protein alfa 4 mezerového spoje * genetika MeSH
- průřezové studie MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- sexuální faktory MeSH
- tlakový index kotník-paže MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- gap junction protein alpha 4, human MeSH Prohlížeč
- protein alfa 4 mezerového spoje * MeSH
Among unique cardiovascular risk factors in women are complications during pregnancy, including miscarriage. Important risk factor is also genetic background. One of powerful candidate genes for cardiovascular disease of atherosclerotic origin (aCVD) is gene for connexin 37 (Cx37) with strong gene-environment interaction including smoking status, that is also strong risk factor for complications in pregnancy including spontaneous abortion (SA). We analyzed association between SA and Cx37 gene polymorphism (1019C>T; Pro319Ser) in 547 fetuses and its potential interaction with smoking status of mothers. Using genetic analyses from women from general population as controls, ORs for T allele, found in our previous studies to be protective against aCVD, were calculated. T allele carriers (fetuses), had OR 0.91 (95 % CI 0.72-1.14) and no interaction with smoking was observed. In conclusion, no significant association between Cx37 polymorphism and SA was observed and no modifying effect of smoking status on this association was detected.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- heterozygot MeSH
- jednonukleotidový polymorfismus MeSH
- konexiny genetika MeSH
- kouření MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- plod MeSH
- polymorfismus genetický MeSH
- protein alfa 4 mezerového spoje MeSH
- rizikové faktory MeSH
- samovolný potrat genetika MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- konexiny MeSH