Interactions of CDKAL1 rs7747752 polymorphism and serum levels of L-carnitine and choline are related to increased risk of gestational diabetes mellitus

Table 5 Additive interactions between rs7747752 and low betaine for gestational diabetes mellitus

SNP	Metabolites	Multivariable model 1		Multivariable model 2
		OR/estimate	P	OR/estimate	P
		(95% CI)	P	(95% CI)	P
Additive interaction between rs7747752 genotypes CG (vs. GG) and low betaine^a
rs7747752	Betaine (in nmol/mL)
GG	>200	1.00	-	1.00	-
GG	≤200	9.00 (3.10–26.1)	<0.001	2.99 (0.84–10.7)	0.092
CG	>200	2.25 (1.20–4.21)	0.011	1.91 (0.90–4.06)	0.093
CG	≤200	8.63 (3.08–24.2)	<0.001	3.64 (0.98–13.5)	0.054
RERI		−1.62 (−13.2 to 9.95)		−0.26 (−5.53 to 5.01)
AP		−0.19 (−1.64 to 1.27)		−0.07 (−1.58 to 1.44)
SI		0.83 (0.21–3.26)		0.91 (0.13–6.24)
Additive interaction between rs7747752 genotypes CC (vs. GG) and low betaine^b
rs7747752	Betaine (in nmol/mL)
GG	>200	1.00	-	1.00	-
GG	≤200	5.30 (2.37–11.9)	<0.001	2.36 (0.82–6.76)	0.109
CC	>200	2.85 (1.31–6.19)	0.008	3.30 (1.31–8.32)	0.011
CC	≤200	24.6 (5.45–111)	<0.001	8.21 (1.44–46.8)	0.018
RERI		17.4 (−18.4 to 53.3)		3.54 (−10.4 to17.4)
AP		0.71 (0.28–1.14)		0.43 (−0.57 to 1.44)
SI		3.83 (0.81–18.1)		1.97 (0.25–15.3)

Multivariable model 2, adjusted for choline at ≤110 vs. >110 nmol/mL and ≤270 vs. >270 nmol/mL and L-carnitine ≤150 nmol/mL, in addition to the variables listed in multivariable model 1
RERI >0, AP >0, or SI >1 indicates a significant additive interaction
Abbreviations: SNP single nucleotide polymorphism, OR odds ratio, CI confidence interval, RERI relative excess risk due to interaction, AP attributable proportion due to interaction, SI synergy index
^aMultivariable model 1, adjusted for traditional risk factors, including pre-pregnancy BMI, family history of diabetes in first-degree relatives, systolic blood pressure, current smoker before pregnancy, gestational weeks at glucose challenge test, and weight gain to the time of glucose challenge test, and further adjusted rs7747752 genotype (CC vs. CG/GG)
^bMultivariable model 1, adjusted for traditional risk factors, including pre-pregnancy BMI, family history of diabetes in first-degree relatives, systolic blood pressure, current smoker before pregnancy, gestational weeks at glucose challenge test, and weight gain to the time of glucose challenge test, and further adjusted rs7747752 genotype (CG vs. CC/GG)

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