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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #334554
Title: Interaction of an S100A9 gene variant with saturated fat and carbohydrates to modulate insulin resistance in 3 populations of different ancestries

Author
item BLANCO-ROJO, RUTH - Reina Sofia University
item DELGADO-LISTA, JAVIER - Universidad De Cordoba
item LEE, YU-CHI - Tufts University
item Lai, Chao Qiang
item PEREZ-MARTINEZ, PABLO - Universidad De Cordoba
item RANGEL-ZUNIGA, ORIOL - Universidad De Cordoba
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HIDALGO, BERTHA - University Of Alabama
item ALCALA-DIAZ, JUAN - Universidad De Cordoba
item GOMEZ-DELGADO, FRANCISCO - Universidad De Cordoba
item Parnell, Laurence
item ARNETT, DONNA - Universidad De Cordoba
item TUCKER, KATHERINE - University Of Massachusetts
item LOPEZ-MIRANDA, JOSE - Universidad De Cordoba
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/9/2016
Publication Date: 8/1/2016
Citation: Blanco-Rojo, R., Delgado-Lista, J., Lee, Y., Lai, C., Perez-Martinez, P., Rangel-Zuniga, O., Smith, C.E., Hidalgo, B., Alcala-Diaz, J.F., Gomez-Delgado, F., Parnell, L.D., Arnett, D.K., Tucker, K.L., Lopez-Miranda, J., Ordovas, J.M. 2016. Interaction of an S100A9 gene variant with saturated fat and carbohydrates to modulate insulin resistance in 3 populations of different ancestries. American Journal of Clinical Nutrition. 104:508–517.

Interpretive Summary: Type 2 diabetes mellitus (T2DM) is an age related disease affecting approximately 400 million people worldwide. T2DM is characterized by a high level of sugar in the blood and resistance to the action of insulin. Complications from T2DM include heart disease, stroke, blindness, kidney failure, and poor blood flow in the extremities, which may lead to amputations. T2DM primarily occurs as a result of poor dietary habits and not enough exercise leading to obesity. Most important, some people are more genetically at risk than others. Several genes have been identified associated with T2DM, one of the latest being the S100 calcium binding protein A9 (S100A9) gene. However, this finding requires validation and in depth analyses in multiple populations and ancestries. Therefore, our aim was to validate the widespread importance of this gene in T2DM and to initiate an investigation of potential interactions with the habitual diet. We investigated the association of the S100A9 gene variant known as rs3014866 with insulin resistance and T2DM risk and its interactions with diet in 3 diverse populations as follows: the CORDIOPREV (Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention; n = 711), which consisted of Spanish white adults; the GOLDN (Genetics of Lipids Lowering Drugs and Diet Network; n = 818), which involved North American non Hispanic white adults; and Hispanic adults who participated in the BPRHS (Boston Puerto Rican Health Study; n = 1155). Our results demonstrate that carriers of the T form of the gene variant (T allele) presented a lower risk of T2DM than CC carriers. Moreover, we showed an interaction between this gene variant and dietary SFA:carbohydrate ratio intake modulating insulin action. CC carriers had a significantly higher risk of T2DM only when SFA:carbohydrate intake was high but not when SFA:carbohydrate ratio intake was low. In conclusion, the T allele of the S100A9 variant rs3014866 is associated with lower T2DM risk in 3 populations of different ancestries. However, those subjects with the CC genotype, who are genetically at risk of T2DM, will benefit from a low SFA:carbohydrate ratio intake to improve insulin resistance. These results may guide personalized recommendations to prevent T2DM and its devastating consequences.

Technical Abstract: BACKGROUND: S100 calcium binding protein A9 (S100A9) has previously been identified as a type 2 diabetes (T2D) gene. However, this finding requires independent validation and more in depth analyses in other populations and ancestries. OBJECTIVES: We aimed to replicate the associations between an S100A9 variant and insulin resistance and T2D and to initiate an investigation of potential interactions with the habitual diet in several independent populations. DESIGN: We investigated the association of the S100A9 variant rs3014866 with insulin resistance and T2D risk and its interactions with diet in 3 diverse populations as follows: the CORDIOPREV (Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention; n = 711), which consisted of Spanish white adults; the GOLDN (Genetics of Lipids Lowering Drugs and Diet Network; n = 818), which involved North American non Hispanic white adults; and Hispanic adults who participated in the BPRHS (Boston Puerto Rican Health Study; n = 1155). RESULTS: Meta analysis indicated that T carriers presented a lower risk of T2D than CC carriers (pooled OR: 0.714; 95% CI: 0.584, 0.845; P = 0.002). In all 3 populations (CORDIOPREV, GOLDN, and BPRHS), we showed a significant interaction between the rs3014866 single nucleotide polymorphism and dietary SFA:carbohydrate ratio intake for the homeostasis model assessment of insulin resistance (HOMA IR) (P = 0.028, P = 0.017, and P = 0.026, respectively). CC carriers had a significantly higher HOMA IR only when SFA:carbohydrate intake was high (P = 0.045 for the CORDIOPREV, P = 0.033 for the GOLDN, and P = 0.046 for the BPRHS) but not when SFA:carbohydrate ratio intake was low. CONCLUSIONS: The minor allele (T) of the S100A9 variant rs3014866 is associated with lower T2D risk in 3 populations of different ancestries. Note that individuals with the high risk CC genotype may be more likely to benefit from a low SFA:carbohydrate ratio intake to improve insulin resistance as evaluated with the use of the HOMA IR.