Single-nucleotide polymorphisms at five loci are associated with C-reactive protein levels in a cohort of Filipino young adults

Curocichin, Ghenadie; Wu, Ying; McDade, Thomas W.; Kuzawa, Christopher W.; Borja, Judith B.; Li, Qin; Lange, Ethan M.; Adair, Linda S.; Lange, Leslie A.; Mohlke, Karen L.

doi:10.1038/jhg.2011.106

Cited by 20 publications

(14 citation statements)

References 33 publications

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“…We recently reported that the frequency and pattern of associations between several SNPs and CRP in young and older adults in the Philippines are consistent with prior research in populations of European ancestry (55,56). The proportion of explained variance in CRP attributable to direct genetic influences was small (4.8-5.6%), with evidence that the level of microbial exposure in the household environment moderated the effects of some of these genes.…”

Section: Early Environments and The Eco-logics Of Inflammationsupporting

confidence: 66%

Early environments and the ecology of inflammation

McDade

2012

Proc. Natl. Acad. Sci. U.S.A.

180

154

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Recent research has implicated inflammatory processes in the pathophysiology of a wide range of chronic degenerative diseases, although inflammation has long been recognized as a critical line of defense against infectious disease. However, current scientific understandings of the links between chronic low-grade inflammation and diseases of aging are based primarily on research in high-income nations with low levels of infectious disease and high levels of overweight/obesity. From a comparative and historical point of view, this epidemiological situation is relatively unique, and it may not capture the full range of ecological variation necessary to understand the processes that shape the development of inflammatory phenotypes. The human immune system is characterized by substantial developmental plasticity, and a comparative, developmental, ecological framework is proposed to cast light on the complex associations among early environments, regulation of inflammation, and disease. Recent studies in the Philippines and lowland Ecuador reveal low levels of chronic inflammation, despite higher burdens of infectious disease, and point to nutritional and microbial exposures in infancy as important determinants of inflammation in adulthood. By shaping the regulation of inflammation, early environments moderate responses to inflammatory stimuli later in life, with implications for the association between inflammation and chronic diseases. Attention to the eco-logics of inflammation may point to promising directions for future research, enriching our understanding of this important physiological system and informing approaches to the prevention and treatment of disease.

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Section: Early Environments and The Eco-logics Of Inflammationsupporting

confidence: 66%

Early environments and the ecology of inflammation

McDade

2012

Proc. Natl. Acad. Sci. U.S.A.

180

154

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“…The magnitude and direction of the effect were fairly consistent across race/ethnicity groups, supporting a jointly consistent association across multiple race/ethnicity groups. Previous studies suggest that SNPs at the APOE/APOC1/TOMM40 locus appear to represent a single signal best represented by rs429358, with other SNPs appearing associated due to correlation 32, 37 . Given the consistency of effect seen in rs429358 across race/ethnicity groups compared to the other SNPs we evaluated in this region, our results appear to support this view, and extend this SNP finding to African Americans and Hispanics.…”

Section: Discussionmentioning

confidence: 99%

Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study

Kocarnik¹,

Pendergrass²,

Carty³

et al. 2014

Circ Cardiovasc Genet

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Background C-reactive protein (CRP) is a biomarker of inflammation. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with CRP concentrations and inflammation-related traits such as cardiovascular disease, type 2 diabetes, and obesity. We aimed to replicate previous CRP-SNP associations, assess whether these associations generalize to additional race/ethnicity groups, and evaluate inflammation-related SNPs for a potentially pleiotropic association with CRP. Methods and Results We selected and analyzed 16 CRP-associated and 250 inflammation-related GWAS SNPs among 40,473 African American, American Indian, Asian/Pacific Islander, European American, and Hispanic participants from 7 studies collaborating in the Population Architecture using Genomics and Epidemiology (PAGE) study. Fixed-effect meta-analyses combined study-specific race/ethnicity-stratified linear regression estimates to evaluate the association between each SNP and high-sensitivity CRP. Overall, 18 SNPs in 8 loci were significantly associated with CRP (Bonferroni-corrected p<3.1×10−3 for replication, p<2.0×10−4 for pleiotropy): Seven of these were specific to European Americans, while 9 additionally generalized to African Americans (1), Hispanics (5), or both (3); 1 SNP was seen only in African Americans and Hispanics. Two SNPs in the CELSR2/PSRC1/SORT1 locus showed a potentially novel association with CRP: rs599839 (p=2.0×10−6) and rs646776 (p=3.1×10−5). Conclusions We replicated 16 SNP-CRP associations, 10 of which generalized to African Americans and/or Hispanics. We also identified potentially novel pleiotropic associations with CRP for two SNPs previously associated with coronary artery disease and LDL cholesterol. These findings demonstrate the benefit of evaluating genotype-phenotype associations in multiple race/ethnicity groups, and of looking for pleiotropic relationships among SNPs previously associated with related phenotypes.

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“…This gene bears binding sites specific for the HNF1A transcription factor. SNPs in HNF1A have been associated to CRP levels in various populations [75][76][77]. Second, although MODY can bear some clinical resemblance with type 2 diabetes, low-grade inflammatory process seen in type 2 diabetes, obesity, and cardiovascular disease does not participate in the pathophysiology of MODY.…”

Section: High-sensitivity C-reactive Protein (Hscrp) and Hnf1amentioning

confidence: 99%

Update on clinical screening of maturity-onset diabetes of the young (MODY)

Peixoto-Barbosa

Reis

Giuffrida

2020

Diabetol Metab Syndr

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Background: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes, being characterized by beta-cell disfunction, early onset, and autosomal dominant inheritance. Despite the rapid evolution of molecular diagnosis methods, many MODY cases are misdiagnosed as type 1 or type 2 diabetes. High costs of genetic testing and limited knowledge of MODY as a relevant clinical entity are some of the obstacles that hinder correct MODY diagnosis and treatment. We present a broad review of clinical syndromes related to most common MODY subtypes, emphasizing the role of biomarkers that can help improving the accuracy of clinical selection of candidates for molecular diagnosis. Main body: To date, MODY-related mutations have been reported in at least 14 different genes. Mutations in glucokinase (GCK), hepatocyte nuclear factor-1 homeobox A (HNF1A), and hepatocyte nuclear factor-4 homeobox A (HNF4A) are the most common causes of MODY. Accurate etiological diagnosis can be challenging. Many biomarkers such as apolipoprotein-M (ApoM), aminoaciduria, complement components, and glycosuria have been tested, but have not translated into helpful diagnostic tools. High-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY and have been tested in some studies to discriminate HNF1A-MODY from other types of diabetes, although more data are needed. Overall, presence of pancreatic residual function and absence of islet autoimmunity seem the most promising clinical instruments to select patients for further investigation. Conclusions: The selection of diabetic patients for genetic testing is an ongoing challenge. Metabolic profiling, diabetes onset age, pancreatic antibodies, and C-peptide seem to be useful tools to better select patients for genetic testing. Further studies are needed to define cutoff values in different populations.

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Single-nucleotide polymorphisms at five loci are associated with C-reactive protein levels in a cohort of Filipino young adults

Cited by 20 publications

References 33 publications

Early environments and the ecology of inflammation

Early environments and the ecology of inflammation

Multiancestral Analysis of Inflammation-Related Genetic Variants and C-Reactive Protein in the Population Architecture Using Genomics and Epidemiology Study

Update on clinical screening of maturity-onset diabetes of the young (MODY)

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