Most cited article - 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.
- Keywords
- Cardiovascular risk factors, Gene for connexin 37, Sex, Type 1 diabetes mellitus, Vascular parameters,
- MeSH
- Diabetes Mellitus, Type 1 * genetics physiopathology MeSH
- Diabetic Angiopathies genetics physiopathology MeSH
- Adult MeSH
- Phenotype MeSH
- Photoplethysmography MeSH
- Genetic Predisposition to Disease MeSH
- Glomerular Filtration Rate MeSH
- Carotid Intima-Media Thickness MeSH
- Middle Aged MeSH
- Humans MeSH
- Polymorphism, Genetic MeSH
- Gap Junction alpha-4 Protein * genetics MeSH
- Cross-Sectional Studies MeSH
- Heart Disease Risk Factors MeSH
- Sex Factors MeSH
- Ankle Brachial Index MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- gap junction protein alpha 4, human MeSH Browser
- Gap Junction alpha-4 Protein * 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
- Biomarkers MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Heterozygote MeSH
- Polymorphism, Single Nucleotide MeSH
- Connexins genetics MeSH
- Smoking MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Fetus MeSH
- Polymorphism, Genetic MeSH
- Gap Junction alpha-4 Protein MeSH
- Risk Factors MeSH
- Abortion, Spontaneous genetics MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- Connexins MeSH