|
| Author | Country | Study populations/mutation | Subjects number | Mutation(s) | Association with birth weight increase | Association with BMI/ obesity | Association with increased insulin levels | Association with diabetes | Conclusions |
|
| Nishigori et al. [111] | Japan | Young-onset type 2 diabetes | 274 | In 7 subjects, 5 different mutations (H53fsdel10, L98fsdel9insAC, R34X, A195S, R213C) and 1 apparent polymorphism (R216H) (all in a heterozygous state) | Yes | Yes | — | No | Shp genetic variation: most common monogenic determinant of obesity and increased birth weight in Japanese |
|
| Hung et al. [110] |
UK | GOOS (severe early-onset obesity) |
329 | R34G and R36C Missense mutations | Yes | No (selection of extreme obesity: stronger effect from other major gene?) | Yes | — | Genetic variation in the SHP locus may influence birth weight and have effects on BMI, possibly through effects on insulin secretion |
| | | |
| G171A (12%) | Yes | — | — |
| | |
| -195CTGAdel (16%) common polymorphisms | No (lower birth weight) | No (lower fasting levels) |
| | | | | | | | |
|
UK | ALSPAC (cohort of children) |
1,079 | G171A | No | Yes (higher BMI and waist circumference at 7 yrs) | Yes (higher fasting levels and 30-min response) | — | Subtle effects in heterozygosity, stronger effects in homozygosity |
| | | |
| -195CTGAdel | No (lower BMI) | |
| | | | | | | |
|
UK | Ely Study (Caucasian adults) |
600 | G171A | Data not available | Yes (BMI increased) | No | — |
| |
| -195CTGAdel | Yes (female: higher BMI),
No (male: lower BMI) |
|
| Mitchell et al. [113] |
UK | Young-onset type 2 diabetes, obesity, birth weight |
1,927 | Birth weight: the only child homozygous for the A allele had a birth weight ≥4 kg | No | No | — | No | Mutations in SHP < UK than in Japanese obese type 2 subjects |
|
| G171A coding polymorphism in 14.1% of UK subjects |
|
| The A allele (G/A genotype) not associated with obesity or increased birth weight |
| Obesity: no association if G/A genotype; yes (?) (if A/A homozygotes) | Yes (?) | Homozygous for the rare A allele: predisposed to moderate obesity and possibly increased birth weight |
|
| Echwald et al. [114] |
Denmark | Early-onset obesity (men) |
750 | 2 silent variants c.65C4T [p. Y22Y], c.339G4A [p. P113P] | — | | — | — | Very low prevalence of functional SHP variants associated with obesity among Danes |
| | |
| 3 missense variants c.100C4G [p. R34G], c.278G4A [p. G93D], c.415C4A [p. P139H] | Yes (only among obese) | A role for G171A polymorphism low penetrance SHP variants) for obesity risk in Europe? |
| | |
| G171A polymorphism (8.9%) | No ( versus obese) | Major differences in prevalence and impact of SHP variants between Danish and Japanese obese |
| | |
| Nonobese controls |
795 | No variants G171A polymorphism (7.1) | |
| | | |
| Functional analyses in MIN6-m9 and HepG2 cell lines | | | 93D mutant protein: reduced in vitro inhibition of the HNF4α transactivation of the HNF-1α promoter expression |
|
