Tenomodulin gene and obesity-related phenotypes

Figures & data

Figure 1. The organization of human tenomodulin gene and protein. Different domains (transmembrane, BRICHOS, and the antiangiogenic domain) are indicated with grey shading. The functional RXXR cleavage site is denoted with an arrow. The locations of the markers used in the different genetic association studies are included. (AD = Alzheimer's disease study; AMD = age-related macular degeneration study; DPS = the Finnish Diabetes Prevention Study; METSIM = the Metabolic Syndrome in Men Study).

Table I. Summary of genetic association studies performed with tenomodulin as a candidate gene.

Phenotype	Study population	Study design	Observed associations	References
Obesity	DPS: 40 – 64 year-old persons with impaired glucose tolerance and overweight (166 men, 341 women)	Life-style intervention, longitudinal	rs11798018-C → higher BMI and weight in menrs5966709-G and rs4828037-T → central obesity in women	(14)
	METSIM: random population-based sample of middle-aged men from Kuopio, Eastern Finland (5298 men)	Cross-sectional	No association	(16)
Glucose metabolism, type 2 diabetes	DPS	Life-style intervention, longitudinal	rs2073163-C and rs1155974-T → higher 2H-PG in men, similar trend in womenrs2073162-A, rs2073163-C, and rs1155974-T → higher incidence of type 2 diabetes in men	(14)
	METSIM	Cross-sectional	No association	(16)
Serum lipoprotein levels	METSIM	Cross-sectional	rs2073162-A → higher total, HDL, and LDL cholesterol levels in men with BMI > median	(16)
	DPS	Cross-sectional (base-line analysis)	rs2073162-A → higher total and LDL cholesterol levels in men with BMI > median	(16)
Serum levels of systemic immune mediators	DPS	Cross-sectional (base-line analysis)	rs2073162-A, rs2073163-C, and rs1155974-T → higher levels of acute phase reactants in menrs5966709-G and rs4828037-T → higher levels of inflammatory factors in men and womenrs2073163-C, rs4828038-T, and rs1155974-T → higher levels of inflammatory factors in women	(15)
Age-related macular degeneration	307 cases (107/200 men/women), 168 controls (55/113 men/women)	Cross-sectional	rs7890586-G, rs2073163-CC, and rs1155974-TT → higher prevalence of (exudative) age-related macular degeneration	(17)
Alzheimer's disease	526 cases (165/361 men/ women), 672 controls (269/403 men/women)	Cross-sectional	rs5966709-T → higher prevalence of Alzheimer's disease among women with apolipoprotein E-IV allele	(18)

DPS = the Finnish Diabetes Prevention Study; METSIM = Metabolic Syndrome in Men Study; 2H-PG = 2-hour plasma glucose concentration.

Table II. The observed associations of the TNMD single-nucleotide polymorphisms with anthropometric measurements in the Finnish Diabetes Prevention Study (DPS). Numeric data are given as median (interquartile range).

Gender	Marker	Genotype	Parameter	Median(IQ range)	P for base-line	P for follow-up
Men	rs11798018	CC	BMI (kg/m^2)	29.70 (4.56)	0.810^a	0.038^a
		AA		29.01 (4.70)
	rs11798018	CC	Weight (kg)	90.30 (16.40)	0.064^a	0.029^a
		AA		86.60 (15.80)
Women	rs2073162	GG	Horizontal diameter (cm)	39.40 (4.25)	0.038^b	0.266^b
		GA		39.20 (5.00)
		AA		38.70 (6.70)
	rs5966709	GG	Waist-to-hip ratio	0.89 (0.08)	0.316^b	0.028^b
		GT		0.89 (0.09)
		TT		0.87 (0.07)
	rs5966709	GG	Sagittal diameter (cm)	24.40 (4.68)	0.080^b	0.014^b
		GT		24.30 (4.30)
		TT		23.00 (3.58)
	rs5966709	GG	Horizontal diameter (cm)	39.20 (5.48)	0.055^b	0.043^b
		GT		39.50 (4.40)
		TT		37.95 (5.53)
	rs5966709	GG	Waist circumference (cm)	99.00 (16.35)	0.068^b	0.036^b
		GT		99.50 (14.50)
		TT		94.35 (19.00)
	rs4828037	TT	Sagittal diameter (cm)	24.40 (4.80)	0.015^b	0.026^b
		TC		24.30 (4.40)
		CC		23.20 (4.10)
	rs4828037	TT	Waist-to-hip ratio	0.89 (0.08)	0.479^b	0.056^b
		TC		0.89 (0.09)
		CC		0.87 (0.07)

^aAdjusted for age.

^bP for additive model adjusted for age and base-line body mass index (BMI).

Table III. The association of the rs207162 of TNMD with serum lipoprotein levels in the men of the Finnish Diabetes Prevention Study (DPS) and the Metabolic Syndrome in Men Study (METSIM). Numeric data are given as median (interquartile range).

			Serum total cholesterol (mmol/L)		Serum HDL Cholesterol (mmol/L)		Serum LDL Cholesterol (mmol/L)
Study population	Strata	Genotype	Median (IQ range)	P	Median (IQ range)	P	Median (IQ range)	P
DPS	1st median	G	5.59 (1.10)	0.112	1.10 (0.32)	0.800	3.67 (1.29)	0.124
	(BMI 23.50–29.40)	A	5.32 (1.43)		1.10 (0.32)		3.53 (1.10)
	2nd median	G	5.26 (1.16)	0.025	0.97 (0.35)	0.866	3.30 (1.13)	0.012
	(BMI 29.45–44.80)	A	5.49 (0.97)		1.05 (0.33)		3.60 (1.06)
METSIM	1st quartile	G	5.23 (1.16)	0.973	1.59 (0.54)	0.315	3.20 (1.01)	0.473
	(BMI 13.18–24.58)	A	5.24 (1.19)		1.57 (0.56)		3.20 (1.15)
	2nd quartile	G	5.31 (1.35)	0.679	1.45 (0.44)	0.566	3.29 (1.23)	0.548
	(BMI 24.59–26.72)	A	5.31 (1.32)		1.45 (0.55)		3.28 (1.09)
	3rd quartile	G	5.31 (1.29)	0.436	1.39 (0.50)	0.472	3.38 (1.26)	0.468
	(BMI 26.73–29.40)	A	5.29 (1.29)		1.37 (0.46)		3.38 (1.14)
	4th quartile	G	5.17 (1.45)	0.009	1.24 (0.39)	0.025	3.23 (1.28)	0.027
	(BMI 29.41–52.11)	A	5.25 (1.47)		1.27 (0.40)		3.37 (1.29)

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