Quantitative trait locus on Chromosome 19 for circulating levels of intercellular adhesion molecule-1 in Mexican Americans

Kent, Jack W.; Mahaney, Michael C.; Comuzzie, Anthony G.; Göring, Harald H.H.; Almasy, Laura; Dyer, Thomas D.; Cole, Shelley A.; MacCluer, Jean W.; Blangero, John

doi:10.1016/j.atherosclerosis.2006.10.005

Cited by 11 publications

(12 citation statements)

References 21 publications

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“…These results were subsequently replicated in large-scale genomics studies from Barbalic [6] et al and Qi [7] et al Nevertheless, the total variance explained by these associations remained low (8.4%) as compared to the relatively high heritability estimates (from 0.34 to 0.59) [8], [9] for sICAM-1. We therefore hypothesized that other, weaker, common genetic determinants of sICAM-1 remained to be discovered.…”

Section: Introductionmentioning

confidence: 73%

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

et al. 2011

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Soluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far. To comprehensively address this issue, we performed a genome-wide association analysis of sICAM-1 concentration in 22,435 apparently healthy women from the Women's Genome Health Study. While our results confirm the previously reported associations at the ABO and ICAM1 loci, four novel associations were identified in the vicinity of NFKBIK (rs3136642, P = 5.4×10−9), PNPLA3 (rs738409, P = 5.8×10−9), RELA (rs1049728, P = 2.7×10−16), and SH2B3 (rs3184504, P = 2.9×10−17). Two loci, NFKBIB and RELA, are involved in NFKB signaling pathway; PNPLA3 is known for its association with fatty liver disease; and SH3B2 has been associated with a multitude of traits and disease including myocardial infarction. These associations provide insights into the genetic regulation of sICAM-1 levels and implicate these loci in the regulation of endothelial function.

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Section: Introductionmentioning

confidence: 73%

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

et al. 2011

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“…Several studies subsequently narrowed down the genetic determinants of circulating sICAM1 levels to the ICAM cluster on chromosome 19 with a heritability estimate from 0.34 to 0.59 [7, 8], and many single nucleotide polymorphisms (SNPs) in the vicinity of the ICAM1 locus were identified to associate with sICAM1 levels [7, 9–11]. We have previously reported that the ICAM1 SNP rs5491 was associated with sICAM1 levels and metabolic syndrome in a Taiwanese population [12].…”

Section: Introductionmentioning

confidence: 99%

Association between NF-κB Pathway Gene Variants and sICAM1 Levels in Taiwanese

Teng

et al. 2017

PLoS ONE

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Intercellular adhesion molecule–1 (ICAM1) is crucial to the development and progression of atherosclerosis. Recent genome-wide association studies (GWAS) have revealed that single nucleotide polymorphisms (SNPs) in two of the nuclear factor-κB (NF-κB) pathway genes, NFKBIK and RELA, are associated with soluble ICAM1 (sICAM1) levels. However, neither of these two gene variants is found in the Asian populations. This study aimed to elucidate whether other candidate gene variants involved in the NF-κB pathway may be associated with sICAM1 levels in Taiwanese. After excluding carriers of the ICAM1 rs5491-T allele, three SNPs in the ICAM1 gene and eight SNPs in six of the NF-κB pathway genes (NFKB1, PDCD11, TNFAIP3, NKAPL, IKBKE, and PRKCB) were analyzed for their association with sICAM1 levels in 480 individuals. Our data showed that two SNPs, rs5498 of ICAM1 and rs1635 of NKAPL, were significantly associated with sICAM1 levels (P = 0.002 and 0.004, respectively) in the Taiwanese population. Using a multivariate analysis, rs5498 and rs1635 as well as the previously reported ABO genotypes and rs12051272 of the CDH13 gene were independently associated with sICAM1 levels (P = 0.001, 0.001, 0.006 and 0.031, respectively). An analysis with combined risk alleles of four candidate SNPs in the ICAM1, NKAPL, ABO, and CDH13 genes showed an increase in sICAM1 levels with added numbers of risk alleles and weighted genetic risk score. Our findings thus expanded the repertoire of gene variants responsible for the regulation of sICAM1 levels in the Asian populations.

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“…39 Linkage analysis detected evidence of linkage to diabetic nephropathy on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3 and to albuminuria on 2q14.1, 7q21.1, and 15q26.3 (unpublished data). Several genome-wide linkage analyses were performed to identify chromosomal regions for CVD risk in the SAFHS 40 . These include leptin concentrations (chromosome 2), 28 cholesterol concentrations in low-density lipoprotein cholesterol size fractions (chromosomes 3 and 4), 41 BMI (chromosome 8), 42 and fasting serum insulin concentrations (chromosome 3).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide scans for microalbuminuria in Mexican Americans: The San Antonio Family Heart Study

Arar

Nath

Thameem

et al. 2007

Genetics in Medicine

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Purpose: Microalbuminuria, defined as urine albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg, is a major risk factor for cardiovascular disease. Several genetic epidemiological studies have established that microalbuminuria clusters in families, suggesting a genetic predisposition. Method: We estimated heritability of microalbuminuria and performed a genome-wide linkage analysis to identify chromosomal regions influencing urine albumin-tocreatinine ratio in 486 Mexican Americans from 26 multiplex families. Results: Significant heritability was demonstrated for urine albumin-to-creatinine ratio (h 2 ϭ 24%, P Ͻ 0.003) after accounting for age, sex, body mass index, triglycerides, and hypertension. Genome scan revealed significant evidence of linkage of urine albumin-tocreatinine ratio to a region on chromosome 20q12 (LOD score of 3.5, P Ͻ 0.001) near marker D20S481. This region also exhibited a LOD score of 2.8 with diabetes status as a covariate and 3.0 with hypertension status as a covariate suggesting that the effect of this locus on urine albumin-to-creatinine ratio is largely independent of diabetes and hypertension. Key Words: Microalbuminuria, albumin to creatinine ratio, cardiovascular diseases, Mexican Americans, family genetic studyMicroalbuminuria is the excretion of low but abnormal levels (Ն30 mg/day) of albumin in the urine. Microalbuminuria is defined as albumin-to-creatinine ratio of 0.03 to 0.299 mg/mg on a random sample of urine. 1 Microalbuminuria is an important independent risk factor for the development of cardiovascular disease (CVD). 2 Several studies have shown that microalbuminuria, in addition to being an independent CVD risk factor, is a significant predictor of CVD, and all-cause mortality in the diabetic and nondiabetic general population. [3][4][5] This predictive effect of microalbuminuria is independent of other known CVD risk factors such as being overweight, hypertension, hypercholesterolemia, and smoking. 6 Results from the Third Copenhagen City Heart Study indicate that even very low levels of microalbuminuria are associated with increased independent risk of CVD. 5 The European Prospective Investigation into Cancer in Norfolk study examined the relationship between microalbuminuria and the incidence of CVD in individuals aged 40 to 79 years without prevalent baseline CVD. Among the participants with baseline CVD, the independent risk of all-cause mortality associated with microalbuminuria increased by 60%, when compared with normoalbuminuric participants, 7 confirming that microalbuminuria is of prognostic value in patients with established CVD. 8 Similarly, results from the San Antonio Heart Study showed that normotensive subjects with microalbuminuria had significantly higher triglyceride concentrations and insulin levels than normotensive Mexican American and non-Hispanic white subjects without microalbuminuria, suggesting that an increased atherogenic risk factor pattern exists even in normotensive subjects with microalbuminuria. 9 In addition, population-based observat...

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Quantitative trait locus on Chromosome 19 for circulating levels of intercellular adhesion molecule-1 in Mexican Americans

Cited by 11 publications

References 21 publications

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

Association between NF-κB Pathway Gene Variants and sICAM1 Levels in Taiwanese

Genome-wide scans for microalbuminuria in Mexican Americans: The San Antonio Family Heart Study

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