Leu72Met Polymorphism in Ghrelin Gene: A Potential Risk Factor for Hypertension in Type 2 Diabetes Patients

Figures & data

Table 1 Demographic and Clinical Profile of Participants with T2DM and Healthy Controls

Variable	T2DM	Controls	p value
N	820	400
Gender (M/W)	451/369	205/195	0.211
Age (years)	65.2 ± 14.4	57.5 ± 8.1	<0.001
Age at DM diagnosis (years)	44.2 ± 7.3	NA	-
T2DM duration (years)	14.1 ± 7.6	NA	-
Cardiovascular disease (%)	603 (73.5)	0	-
Hypertension (%)	582 (71)	0	-
BMI (kg/m^2)	29.3 ± 5.6	27.1 ± 4.2	<0.001
SBP (mmHg)	145 ± 16.3	123 ± 11.3	<0.001
DBP (mmHg)	84 ± 11.6	75 ± 9.7	<0.001
TC (mmol/l)	4.9 ± 2.3	4.0 ± 0.78	<0.001
HDL cholesterol (mmol/l)	1.2 ± 0.4	ND	-
TG (mmol/l)	2.2 ± 1.19	1.2 ± 0.63	<0.001
HbA1c % (mmol/mol)^a	8.7 ± 2.1 (72 ± 6)	ND	-

Notes: Values are presented as means ± SD for continuous characteristics and numbers (%) for discrete characteristics. Values compared between groups by Mann–Whitney and Pearson’s Χ² tests. ^aThe data were missing for 21 persons (2.5%) and they were replaced with a mean for T2DM group.

Abbreviations: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglycerides.

Table 2 Genotype and Allele Distribution of Leu72Met Polymorphism in the GHRL Gene in Participants withT2DM and Healthy Individuals

	Genotypes				MAF	HWE	OR (95% CI)
	N	GG	GT	TT			T Allele	TT Genotype^a
T2DM	820	632 (77)	172 (21)	16 (2)	0.12	0.288	1.14 (0.88–1.49)	1.01 (0.42–2.39)
							p = 0.304	p = 0.977
Controls	400	320 (80)	72 (18)	8 (2)	0.11	0.106	Ref.	Ref.

Notes: Genotype distribution is shown as numbers (%). Hardy–Weinberg equilibrium: χ² = 2.604, p = 0.106 for control group; χ² = 1.127, p = 0.288 for participants with T2DM. ^aCalculated versus GG genotype.

Abbreviations: T2DM, type 2 diabetes mellitus; GHRL, ghrelin; MAF, minor allele frequency.

Table 3 Distribution of the GHRL Gene Leu72Met Polymorphism According to the Model of Inheritance

GHRL Leu72Met Genotypes	T2DM (n = 820)	Controls (n = 400)	OR (95% CI)	p value
Codominant model
GG	632	320	Ref.	–
GT	172	72	1.20 (0.89–1.64)^a	0.223
TT	16	8	1.01 (0.42–2.39)^a	0.977
Dominant model
GG	632	320	Ref.	–
GT + TT	188	80	1.18 (0.88–1.59)^a	0.246
Recessive model
GG + GT	804	392	Ref.	–
TT	16	8	0.97 (0.41–2.29)^b	0.954

Notes: Genotype distribution is presented as numbers. Odds ratios are referred to ^aGG homozygote and ^bGG+GT genotypes.

Abbreviations: GHRL, ghrelin gene. T2DM, type 2 diabetes mellitus.

Table 4 The Results of Multivariate Logistic Regression Analysis

Variable	Odds Ratio	95% CI	p value
Age at study	1.21	0.69–1.33	0.067
Gender	1.16	0.62–1.81	0.042
T2DM duration	1.27	0.54–2.06	0.216
Age at T2DM onset	1.09	0.46–2.11	0.532
BMI	1.14	0.73–1.29	0.608
T allele*	2.36	1.61–3.53	<0.001

Notes: *GHRL rs696217 polymorphism. An unconditional model of multiple logistic regression analysis was carried out for interaction between GHRL gene polymorphism and other variables.

Abbreviation: T2DM, type 2 diabetes mellitus.

Table 5 Genotype and Allele Distribution of Leu72Met Polymorphism in the GHRL Gene in Participants with T2DM with Different Clinical Phenotypes

	Genotypes					OR (95% CI)
	N	GG	GT	TT	MAF	T allele	TT Genotype^a
T2DM HY+	582	423 (72)	145 (25)	14 (3)	0.15	2.50 (1.68–3.73) p < 0.001^b	3.45 (0.77–15.35) p = 0.102
T2DM HY-	238	209 (88)	27 (11)	2 (1)	0.06	Ref.	Ref.
T2DM DN+	392	294 (74)	90 (23)	8 (3)	0.14	1.20 (0.90–1.62) p = 0.204	1.14 (0.42–3.10) p = 0.783
T2DM DN-	428	338 (79)	82 (19)	8 (2)	0.11	Ref.	Ref.
T2DM OW/OB	493	372 (75)	112 (23)	9 (2)	0.13	1.19 (0.87–1.61) p = 0.261	0.90 (0.33–2.44) p = 0.834
T2DM Non-OB	327	260 (80)	60 (18)	7 (2)	0.11	Ref.	Ref.

Notes: Genotype distribution is shown as numbers (%). ^aCalculated versus GG genotype. ^bAfter adjusting for age, gender and BMI, OR = 2.62, 95% CI 1.83–3.96 (p < 0.001).

Abbreviations: T2DM, type 2 diabetes mellitus; GHRL, ghrelin; HY, hypertension; DN, diabetic nephropathy; OW/OB, overweight/obese (BMI 27–36 kg/m²); Non-OB, non-obese (BMI <27 kg/m²); MAF, minor allele frequency.