Sex-specific interactions between the IRS1 polymorphism and intakes of carbohydrates and fat on incident type 2 diabetes

Ericson, Ulrika; Rukh, Gull; Stojkovic, Ivana; Sonestedt, Emily; Gullberg, Bo; Wirfält, Elisabet; Wallström, Peter; Orho‐Melander, Marju

doi:10.3945/ajcn.112.046474

Cited by 29 publications

(39 citation statements)

References 37 publications

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“…Consistent with those observations, the results were replicated in the women of MESA African-American, non-Hispanic white, and Hispanic populations. The genetic effect of IRS1 variant rs2943641 on IR and T2D was susceptible to various dietary factors, as has been demonstrated in 3 other studies (7, 26, 27). One intervention study (7) found that rs2943641 interacted with dietary carbohydrate and fat on IR, and that rs2943641 CC carriers saw more benefit in terms of improved insulin sensitivity when choosing a high-carbohydrate and low-fat diet.…”

Section: Discussionsupporting

confidence: 68%

“…In contrast, Zheng and colleagues (27) found that rs2943641 T allele carriers had lower risk of IR and metabolic syndrome when their dietary saturated fat-to-carbohydrate ratio was low. Another recent observational study (26) suggested a 3-way interaction between sex, rs2943641, and carbohydrate intake on incident T2D, and men and women showed opposite directions of the interaction between rs2943641 and carbohydrate intake. Our present study reports an interaction of rs2943641 with status of a micronutri-ent (vitamin D) on insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…As a sex-specific interaction between the IRS1 variant rs2943641 and dietary factors on risk of type 2 diabetes was observed in a prior report (26), statistical analysis was performed in men and women separately in both BPRHS and MESA. As significant interactions for T2D or T2D-related traits were observed only among women, only the results from women participants are reported in our present study.…”

Section: Methodsmentioning

confidence: 99%

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Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene–Nutrient Interaction in 4 Populations of Different Ancestries

et al. 2014

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BACKGROUND Associations of either insulin receptor substrate 1 (IRS1) variants or circulating 25-hydroxyvitamin D [25(OH)D] with type 2 diabetes (T2D) and insulin resistance (IR) are inconsistent. This study sought to determine whether circulating 25(OH)D modulates the association of a potentially functional variant at IRS1 (rs2943641) with insulin resistance. METHOD Interaction between IRS1 rs2943641 and circulating 25(OH)D on homeostasis model assessment for IR (HOMA-IR) was examined in the Boston Puerto Rican Health Study (BPRHS) (n = 1144). Replication was performed in the African-American (n = 1126), non-Hispanic white (n = 1967), and Hispanic (n = 1241) populations of the Multi-Ethnic Study of Atherosclerosis (MESA) with genotypes of 3 IRS1 variants, rs2972144, rs1515104, and rs2673142, which are tag single nucleotide polymorphisms (SNPs) and in strong linkage disequilibrium with rs2943641. RESULTS Higher circulating 25(OH)D was associated with lower risk of T2D and IR in BPRHS women homozygous for minor allele rs2943641T. Consistently, in each of 3 MESA populations, HOMA-IR and insulin decreased more evidently with higher circulating 25(OH)D in women of the rs2943641TT genotype than in carriers of the major allele (rs2943641C). Metaanalysis indicated significant and consistent interactions between circulating 25(OH)D and IRS1 variants on HOMA-IR (log transformed) [pooled β = −0.008, 95% CI: −0.016 to −0.001, P interaction = 0.004] and insulin (log transformed) (pooled β = −0.006, 95% CI: −0.011 to −0.002, P interaction = 0.023) in 3065 women of the 4 populations. CONCLUSIONS Participants with different genotypes of IRS1 rs2943641 exhibit differential benefit from high circulating 25(OH)D for the reduction of insulin resistance and T2D risk. This gene–nutrient interaction, which appears to be limited to women, warrants further examination in randomized controlled trials of vitamin D supplementation.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene–Nutrient Interaction in 4 Populations of Different Ancestries

et al. 2014

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“…Nine articles [17][18][19][20][21][22][23][24][25] were excluded from the systematic review because of overlapping populations. Out of these 22 articles, a total of 13 cohort studies [26][27][28][29][30][31][32][33][34][35][36][37][38] were appraised in the systematic review and metaanalysis. The 13 selected articles included in the systematic review were moderately heterogeneous in terms of population demographics, carbohydrate intake parameters, and the assessment of confounding factors.…”

Section: Search Resultsmentioning

confidence: 99%

“…Although the majority of the enrolled subjects were middle-aged and free of chronic disease at baseline, healthcare professionals were predominant in the US cohorts and might not have been truly representative of the average population in the community. In two cohorts consisting exclusively of men 33,34 and another cohort, 36 the risks of diabetes were significantly elevated among the subjects with low-carbohydrate diets (relative risk range, 1.15-1.31). In contrast, the risks in women 30,31,38 were significantly lower (relative risk range, 0.63-0.79).…”

Section: Qualitative Summarymentioning

confidence: 99%

Long‐term Low‐carbohydrate Diets and Type 2 Diabetes Risk: A Systematic Review and Meta‐analysis of Observational Studies

Noto

Goto

Tsujimoto

et al. 2016

J of Gen and Family Med

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Objective: Low-carbohydrate diets have favorable short-term effects on body weight and risk factors for cardiovascular disease. However, they are potentially associated with an increased long-term risk of mortality. Our objective was to elucidate their effects on the incidence of diabetes.Methods: Several databases (MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov) were searched for relevant articles that were published prior to May 2015. Cohort studies with a follow-up period of at least one year were included. Identified articles were systematically reviewed, and those with pertinent data were selected for inclusion in a meta-analysis. The pooled risk ratio (RR) with 95% confidence interval (CI) for the incidence of diabetes was calculated using the random-effects model with inverse-variance weighting.Results: We included 13 studies in a systematic review, followed by a meta-analysis using pertinent data. Among the 440,669 people that were included in 11 cohort studies, 27,887 (6.3%) cases of diabetes were documented. The risk of incident diabetes among individuals with a low-carbohydrate diet was not significantly different from that of individuals with a high-carbohydrate diet: the pooled RR was 1.03 (95% CI, 0.91-1.16). Journal of General and Family Medicine 2016, vol. 17, no. 1, p. 60-70. Review Articles -60 -Conclusion: Low-carbohydrate diets did not show any benefit on the risk of diabetes. However, this analysis is based on limited observational studies, and large-scale trials examining the complex interactions between low-carbohydrate diets and long-term outcomes are needed.

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Validation in a Brazilian population of gene markers of periodontitis previously investigated by GWAS and bioinformatic studies

Cirelli

Nepomuceno

Orrico

et al. 2020

Journal of Periodontology

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Background: Bioinformatic tools and genome-wide association studies (GWAS) have led to comprehensive identification of single nucleotide polymorphisms (SNPs) associated with periodontitis in diverse populations. Here we aimed to detect and validate the association of seven SNPs as genetic markers of susceptibility to periodontitis in a Brazilian population. Methods: This case-control study assessed complete periodontal parameters of 714 subjects with periodontal status classified as healthy/mild periodontitis (n = 356) and moderate/severe periodontitis (n = 358). Genotyping for rs187238, rs352140, rs1360573, rs2521634, rs3811046, rs3826782, and rs7762544 SNPs were evaluated. Genetic-phenotype associations, and sex or smoking effects of SNPs on periodontitis were tested using multiple logistic regressions adjusted for covariates. Results: The rs2521634-AA (close to NPY gene) presented increased risk for severe periodontitis (OR = 2.34; 95% CI = 1.19-4.59). The rs3811046-GG (IL37 gene) demonstrated increased risk for moderate periodontitis (OR = 2.58; 95% CI = 1.28-5.18). Higher risk for moderate periodontitis was found in male with rs7762544-AG close to NCR2 gene. The rs352140-TT in the TLR9 gene proved to be associated with lower risk to severe periodontitis in men. The rs2521634-AA was associated with higher percentage of interproximal probing pocket depth (P = .004).Conclusions: This is the first evidence of validation in a Brazilian population of genetic markers of periodontitis previously investigated by GWAS and bioinformatics studies. SNPs in the NPY, IL37, and NCR2 genes were associated with susceptibility to moderate or severe periodontitis; whereas the TLR9 marker was associated with lower chance to develop severe periodontitis. Those SNPs had sex-and smoking-habit-specific effects on periodontitis; reinforcing the genetic profile predisposing to periodontitis.

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Sex-specific interactions between the IRS1 polymorphism and intakes of carbohydrates and fat on incident type 2 diabetes

Abstract: Our results indicate that IRS1 rs2943641 interacts with carbohydrate and fat intakes on incident T2D in a sex-specific fashion. A protective association between the rs2943641 T allele and T2D was restricted to women with low carbohydrate intake and to men with low fat intake.

Cited by 29 publications

References 37 publications

Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene–Nutrient Interaction in 4 Populations of Different Ancestries

Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene–Nutrient Interaction in 4 Populations of Different Ancestries

Long‐term Low‐carbohydrate Diets and Type 2 Diabetes Risk: A Systematic Review and Meta‐analysis of Observational Studies

Validation in a Brazilian population of gene markers of periodontitis previously investigated by GWAS and bioinformatic studies

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