TABLE 2.
Association between SNPs within the MC4R gene locus and total energy, carbohydrate, and fat intakes1
| SNP and study type | Study population | Study characteristics according to methods and results sections | n (M/F) | Dietary assessment | Dietary data | P | Results | First author (year) (ref) |
|---|---|---|---|---|---|---|---|---|
| rs177823132 | ||||||||
| Cross-sectional study | Not specified (Iranian study) | Mean age according to genotype: TT = 43.5 ± 12.4 y, CT = 45.7 ± 13.0 y, CC = 42.4 ± 12.1 y | 374 (170/204) | 3-d food record | Energy (kcal/d) | <0.0013 | CC genotype higher energy intake than TT (ß = 217.7 kcal/d) | Khalilitehrani et al. (2015) (44) |
| Carbohydrate (g/d) | <0.0014 | CC genotype lower carbohydrate intake than TT (ß = –29.99 g/d) | ||||||
| Fat (g/d) | 0.2004 | |||||||
| BMI < 25 | 155 (71/84) | Energy (kcal/d) | 0.8603 | |||||
| Carbohydrate (g/d) | 0.0404 | CC genotype lower carbohydrate intake than TT (ß = –17.56 g/d) | ||||||
| Fat (g/d) | 0.0904 | |||||||
| BMI ≥ 25 | 219 (99/120) | Energy (kcal/d) | <0.0013 | CC genotype higher energy intake than TT (ß = 379.8 kcal/d) | ||||
| Carbohydrate (g/d) | <0.0014 | CC genotype lower carbohydrate intake than TT (ß = –39.11 g/d) | ||||||
| Fat (g/d) | 0.7304 | |||||||
| Cross-sectional study (meta-analysis) | White, African American, Asian | Age range: 31–75 y; BMI range: 22.1–31.6 | 177,330 (62,275/115,055) | FFQ, dietary record, recall | Energy (kcal/d) | 0.6605 | Qi et al. (2014) (30) | |
| Carbohydrate (%E) | 0.5905 | |||||||
| Fat (%E) | 0.0805 | |||||||
| Postprandial study | Not specified (English study) | Mean age: 32.1 ± 9.1 y; mean BMI: 26.8 ± 1.6 | 40 (40/0) | Ad libitum lunch | Energy (kJ/d) | 0.4736 | Dougkas et al. (2013) (31) | |
| Cross-sectional study (meta-analysis) | African American, Asian American, Latino, Pacific Islander, European American, other | NA | 36,973 | FFQ, 24-h dietary recall | Energy (kcal/d) | 0.8307 | Park et al. (2013) (39) | |
| Carbohydrate (%E) | 0.8007 | |||||||
| Fat (%E) | 0.4607 | |||||||
| African American, Asian American, Latino, Pacific Islander, European American (MEC) | Mean age: 68 y (62–74 y); mean BMI: 26.1 (23.6–29.2) | 19,529 (10,096/9433) | FFQ | Energy (kcal/d) | NS | |||
| Carbohydrate (%E) | NS | |||||||
| Fat (%E) | NS | |||||||
| African American, European American (CALiCo: ARIC) | Mean age: 54 y (49–59 y); mean BMI: 26.4 (23.7–29.8) | 11,114 (4957/6157) | FFQ | Energy (kcal/d) | NS | |||
| Carbohydrate (%E) | NS | |||||||
| Fat (%E) | NS | |||||||
| African American, Latino, European American (EAGLE-NHANES III) | Mean age: 54 y (49–59 y); mean BMI: 26.4 (23.7–29.8) | 6347 (2767/3580) | 24-h recall | Energy (kcal/d) | NS | |||
| Carbohydrate (%E) | NS | |||||||
| Fat (%E) | NS | |||||||
| Cross-sectional study | Not specified (Swedish study) | Mean age: 58.0 ± 7.6y; mean BMI: 25.8 ± 4.1 | 29,480 (11,754/17,726) | 7-d menu book, FFQ | Energy (kcal/d) | 0.5808 | Rukh et al. (2013) (32) | |
| Carbohydrate (%E) | 0.6808 | |||||||
| Fat (%E) | 0.9908 | |||||||
| Cross-sectional study | African American, American Indian/Alaska Native, Asian/Pacific Islander, white, other | Patients with type 2 diabetes; mean age: 57.6 ± 7.2 y; mean BMI: 36.3 ± 6.1 | 2075 (912/1163) | FFQ | Energy (kcal/d) | 0.6849 | McCaffery et al. (2012) (35) | |
| Carbohydrate (%E) | 0.97410 | |||||||
| Fat (%E) | 0.91010 | |||||||
| Cross-sectional study | Dutch | Mean age: 57.2 ± 6.1 y; mean BMI: 25.9 ± 4.0 | 1700 (0/1700) | FFQ | Energy (kcal/d) | 0.480 | Bauer et al. (2009) (43) | |
| Carbohydrate (g/d) | 0.39011 | |||||||
| Fat (g/d) | 0.78011 | |||||||
| Cohort study | White (European ancestry) | Mean age: 54.1 ± 6.7 y | 5724 (0/5724) | FFQ | Energy (kcal/d) | 0.00912 | CC genotype had higher total energy intake than TT genotype (ß = 84 kcal/d) | Qi et al. (2008) (45) |
| Carbohydrate (g/d) | 0.11012 | |||||||
| Carbohydrate (%E) | 0.45012 | |||||||
| Fat (g/d) | 0.00112 | CC genotype had higher total fat intake than TT genotype (ß = 4.6 g/d) | ||||||
| Fat (%E) | 0.14012 | |||||||
| rs17700633 | ||||||||
| Cross-sectional study | Dutch | Mean age: 57.2 ± 6.1 y; mean BMI: 25.9 ± 4.0 | 1700 (0/1700) | FFQ | Energy (kcal/d) | 0.830 | Bauer et al. (2009) (43) | |
| Carbohydrate (g/d) | 0.94011 | |||||||
| Fat (g/d) | 0.83011 | |||||||
| Cohort study | White (European ancestry) | Severe obesity; mean age: 44.3 ± 11.4 y; mean BMI: 46.0 ± 7.6 | 5724 (0/5724) | FFQ | Energy (kcal/d) | NS | Qi et al. (2008) (45) | |
| Carbohydrate (g/d) | NS | |||||||
| Carbohydrate (%) | NS | |||||||
| Fat (g/d) | NS | |||||||
| Fat (%) | NS | |||||||
| rs17700144 | ||||||||
| Cross-sectional study | German | Mean age: 49.4 ± 14.0 y; mean BMI: 27.0 ± 4.5 | 12,462 (6271/6191) | FFQ | Carbohydrate (score) | 0.19013 | Holzapfel et al. (2010) (42) | |
| Fat (score) | 0.95013 | |||||||
| rs2229616 | ||||||||
| Cross-sectional study | Not specified (white persons from Utah) | Severe obesity; mean age: 44.3 ± 11.4 y; mean BMI: 46.0 ± 7.6 | 1029 (191/838) | FFQ | Energy (kcal/d) | 0.83014 | Pichler et al. (2008) (46) | |
| Carbohydrate (g/d) | 0.01015 | Carriers of the variant showed higher carbohydrate intakes than did homozygote wild-type carriers (57 g/d) | ||||||
| Fat (g/d) | 0.13016 | |||||||
| rs571312 | ||||||||
| Cross-sectional study | Diverse racial and ethnic groups (non-Hispanic white, African American, Hispanic, Asian/Pacific Islander, American Indian) | Participants with impaired glucose tolerance and at high risk of diabetes; mean age: 50.8 ± 10.6 y; mean BMI: 34.0 ± 6.6 | 3180 (1047/2133) | FFQ | Energy (kcal/d) | 0.01817 | Greater total caloric intake per copy minor T allele (ß = 58.84 kcal/d) | McCaffery et al. (2017) (38) |
| Carbohydrate (%E) | NS | |||||||
| Fat (%E) | NS | |||||||
| Non-Hispanic white | 1796 (56.5% female) | FFQ | Energy (kcal/d) | 0.17217 | ||||
Values are means ± SDs unless otherwise indicated. BMI unit: kg/m2. Main results of studies concerning the association between MC4R and total energy, carbohydrate, and fat intakes are shown. SNPs are sorted by number of publications and publication date. Details in the table are stated as mentioned in the article. Some SNPs are in a high LD (r2 > 0.8) to each other. The LD values described by r² were calculated by using a Web tool (25); the LD plot is shown in Supplemental Figure 2. CALiCo: ARIC, Causal Variants Across the Life Course and Atherosclerosis Risk in Communities Study Consortium; EAGLE, Epidemiologic Architecture for Genes Linked to Environment; GWAS, genomewide association study; LD, linkage disequilibrium; MC4R, melanocortin 4 receptor; MEC, Multi-Ethnic Cohort; NA, not available; ref, reference; SNP, single nucleotide polymorphism; %E, percentage of energy.
r² to rs571312 = 0.96.
Adjusted for age, sex, physical activity, and smoking status.
Adjusted for age, sex, physical activity, smoking status, and energy intake.
Adjusted for age, geographical region (if available), physical activity (if available), and eigenvectors (GWAS data only).
Adjusted for age, BMI, baseline appetite scores, visit, and treatment.
Adjusted for age at blood draw, sex, and race/ethnicity.
Adjusted for age, sex, season, and diet assessment method (values for carbohydrate and fat intake are additionally adjusted for energy).
Adjusted for age, sex, study site, population stratification, and weight.
Adjusted for age, sex, study site, and population stratification.
Adjusted for energy.
Adjusted for age, BMI, and diabetes status.
Adjusted for age, sex, and survey.
Adjusted for age, sex, and carbohydrate intake.
Adjusted for age, sex, and BMI.
Adjusted for age and sex.
Adjusted for age, sex, study site, weight, and principal components reflecting genetic ancestry.