Haplotypes in the<i>CRP</i>Gene Associated with Increased BMI and Levels of CRP in Subjects with Type 2 Diabetes or Obesity from Southwestern Mexico

Martínez-Calleja, América; Quiróz-Vargas, Irma; Parra‐Rojas, Isela; Muñoz‐Valle, José Francisco; Leyva‐Vázquez, Marco Antonio; Fernández‐Tilapa, Gloria; Vences-Velázquez, Amalia; Cruz, Miguel; Salazar-Martı́nez, Eduardo; Flores‐Alfaro, Eugenia

doi:10.1155/2012/982683

Cited by 21 publications

(18 citation statements)

References 32 publications

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“…This is an important topic because CRP levels may be related to CRP gene mutations. Previous studies demonstrated that CRP levels were associated with different CRP alleles and haploids . Our study showed that CRP levels were similar with and without CRP gene polymorphism.…”

Section: Discussionsupporting

confidence: 74%

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The relationship between C‐reactive protein rs3091244 polymorphism and ankylosing spondylitis

et al. 2015

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Section: Discussionsupporting

confidence: 74%

“…performed a large population study showing that the presence of a CRP minor allele was related to lower CRP levels in hypertensive patients. In a Mexican population, large sample studies by Martínez‐Calleja et al . showed that the CRP gene polymorphism was related to increased CRP levels and was a cardiovascular risk factor.…”

Section: Introductionmentioning

confidence: 99%

The relationship between C‐reactive protein rs3091244 polymorphism and ankylosing spondylitis

et al. 2015

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“…Y. However, Martínez-Calleja et al (2012) showed that one of these SNPs (rs1130864) is directly related to BMI, and it is also known that there exists a negative association between higher levels of BMI and HDL (Shamai et al, 2011). Hence, these 3 SNPs may not all be valid instruments for causal effect estimation of CRP protein levels on HDL.…”

Section: Approaches Based On 2slsmentioning

confidence: 99%

Constrained Instruments and their Application to Mendelian Randomization with Pleiotropy

Jiang

Oualkacha

Didelez

et al. 2017

Preprint

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In Mendelian randomization (MR), genetic variants are used to construct instrumental variables, which enable inference about the causal relationship between a phenotype of interest and a response or disease outcome. However, standard MR inference requires several assumptions, including the assumption that the genetic variants only influence the response through the phenotype of interest. Pleiotropy occurs when a genetic variant has an effect on more than one phenotype; therefore, a pleiotropic genetic variant may be an invalid instrumental variable. Hence, a naive method for constructing instrumental variables may lead to biased estimation of the causality between the phenotype and the response. Here, we present a set of intuitive methods (Constrained Instrumental Variable methods [CIV]) to construct valid instrumental variables and perform adjusted causal effect estimation when pleiotropy exists, focusing particularly on the situation where pleiotropic phenotypes have been measured. Our approach includes an automatic and valid selection of genetic variants when building the instrumental variables. We also provide details of the features of many existing methods, together with a comparison of their performance in a large series of simulations. CIV methods performed consistently better than many comparators across four different pleiotropic violations of the MR assumptions. We analyzed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Mueller et al. (2005) to disentangle causal relationships of several biomarkers with AD progression. The results showed that CIV methods can provide causal effect estimates, as well as selection of valid instruments while accounting for pleiotropy.

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“…Polymorphisms located in promoter regions, including rs2794521 (-717 A/G) of CRP gene, -572 C/G (rs1800796) of IL6 gene and -1031 T/C (rs1799964) of TNF gene, have been associated with T2DM risk [7,[9][10][11][12][13]. Several studies demonstrated a notable in uence of the rs2794521 polymorphism on CRP secretion [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies demonstrated a notable in uence of the rs2794521 polymorphism on CRP secretion [14][15][16]. Alteration of CRP concentration may modify T2DM risk [5][6]9]. Similarly, the rs1800796 IL6 polymorphism was postulated to affect the expression of interleukin 6 [11,17] which can initiate insulin resistance and eventually T2DM [3].…”

Section: Introductionmentioning

confidence: 99%

A transition of C to G (rs1800796) at promoter region of IL6 gene is associated with lowered risk of elevated blood glucose in rural Thais

Phosat

Phienluphon

Hananantachai

et al. 2019

Preprint

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Background Inflammation has been associated with increased risk of type 2 diabetes mellitus (T2DM). Thus, polymorphisms of genes encoding pro-inflammatory cytokines may influence the condition. This study aimed to determine the association between genetic variations in inflammation-related genes, including rs2794521 of the CRP gene, rs1800796 of the IL6 gene, and rs1799964 of the TNF gene, and risk of elevated blood glucose.Methods A total of 296 subjects were allocated to either the control group (n=135) or elevated blood glucose group (n=161). The studied single nucleotide polymorphisms were investigated among 296 subjects by real-time PCR technique. Logistic regression model was used to evaluate the association between the genetic variations and risk of elevated blood glucose.Results Both dietary intake and concentrations of inflammatory cytokines (CRP, IL6, and TNF-α) in the subjects with different genotypes were analogous. AG carriers of rs2794521 CRP showed the highest levels of obesity indices (BMI, waist circumference, and body fat; p<0.05 for all) compared to wild type. Homozygous variants of rs1800796 (GG) and rs1799964 (CC) were associated with significantly lower HbA1c level ( p =0.041) and fasting blood glucose concentration ( p =0.043), respectively. An association with decreased risk of elevated blood glucose was found among GG female carriers of rs1800796 [OR 0.23 (0.06-0.87), p =0.031]. A tendency towards lowered blood glucose was also seen in AGT carriers [OR 0.49 (0.024-1.02), p =0.058).Conclusions The polymorphisms rs2794521 CRP, rs1800796 IL6, and rs1799964 TNF were associated with risk of T2DM. Individuals who carried GG of rs1800796 or -717A-572G-1031T displayed a lower risk of T2DM.

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Haplotypes in theCRPGene Associated with Increased BMI and Levels of CRP in Subjects with Type 2 Diabetes or Obesity from Southwestern Mexico

Cited by 21 publications

References 32 publications

The relationship between C‐reactive protein rs3091244 polymorphism and ankylosing spondylitis

The relationship between C‐reactive protein rs3091244 polymorphism and ankylosing spondylitis

Constrained Instruments and their Application to Mendelian Randomization with Pleiotropy

A transition of C to G (rs1800796) at promoter region of IL6 gene is associated with lowered risk of elevated blood glucose in rural Thais

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