TY - JOUR
T1 - Acanthosis nigricans as a composite marker of cardiometabolic risk and its complex association with obesity and insulin resistance in Mexican American children
AU - Lopez-Alvarenga, Juan C.
AU - Chittoor, Geetha
AU - Paul, Solomon F.D.
AU - Puppala, Sobha
AU - Farook, Vidya S.
AU - Fowler, Sharon P.
AU - Resendez, Roy G.
AU - Hernandez-Ruiz, Joselin
AU - Diaz-Badillo, Alvaro
AU - Salazar, David
AU - Garza, Doreen D.
AU - Lehman, Donna M.
AU - Mummidi, Srinivas
AU - Arya, Rector
AU - Jenkinson, Christopher P.
AU - Lynch, Jane L.
AU - DeFronzo, Ralph A.
AU - Blangero, John
AU - Hale, Daniel E.
AU - Duggirala, Ravindranath
N1 - Funding Information:
Funding: This study was supported RD received grants: R01 HD049051/HD049051-5S1 [ARRA], HD041111, DK053889, DK042273, DK047482, MH059490, P01 HL045522, K01 DK064867, M01-RR- 01346, and Veterans Administration Epidemiologic Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Some of the investigators received salaries from some of the grants as follows: R01 HD049051/HD049051-5S1 [ARRA] (RD, DEH, JB, RAD, CPJ, RA, SP, VSF, SPF, RGR), HD041111 (RD, JB, RAD, CPJ, RA, RGR), DK053889 (RD, JB, CPJ, SP, VSF, SPF, RGR), DK042273 (DML, RD, JB), DK047482 (DML), MH059490 (JB), P01 HL045522 (JB, RD), and Veterans Administration Epidemiologic Grant (RAD, CPJ). The AT&T Genomics Computing Center supercomputing facilities used for this work were supported in part by a gift from the AT&T Foundation and with support from the National Center for Research Resources Grant Number S10 RR029392. This investigation was conducted in facilities constructed with support from Research Facilities Improvement Program grants C06 RR013556 and C06 RR017515 from the National Center for Research Resources of the National Institutes of Health.
Publisher Copyright:
Copyright: © 2020 Lopez-Alvarenga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/10
Y1 - 2020/10
N2 - Aim Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). Methods We used data from 670 non-diabetic MA children, aged 6–17 years (49% girls). AN (prevalence 33%) severity scores (range 0–5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. Results Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI!HOMA-IR!AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. Conclusion Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.
AB - Aim Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). Methods We used data from 670 non-diabetic MA children, aged 6–17 years (49% girls). AN (prevalence 33%) severity scores (range 0–5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. Results Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI!HOMA-IR!AN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. Conclusion Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.
UR - http://www.scopus.com/inward/record.url?scp=85092795261&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092795261&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0240467
DO - 10.1371/journal.pone.0240467
M3 - Article
C2 - 33057385
AN - SCOPUS:85092795261
SN - 1932-6203
VL - 15
JO - PLoS One
JF - PLoS One
IS - 10 October
M1 - e0240467
ER -