Table 8.

Association of HLA Amino Acid Positions with Multiple Sclerosis

A. Association of Variant DRB1 Exon-2 encoded Amino Acid Positions, HLA-B Amino Acid position 80, and HLA-C Amino Acid positions 73, 77, 80 and 90 with Multiple Sclerosis.
Locus	Variant Amino Acid Position	X.square	d.f.	p-value	Significance 1
DRB1	10	0.8016	2	6.70E−01	NS
DRB1	11	110.594	5	< 2.22e−16	*
DRB1	12	0.6384	1	4.24E−01	NS
DRB1	13	113.1725	5	< 2.22e−16	*
DRB1	14	11.6544	1	6.41E−04	*
DRB1	16	3.5177	1	6.07E−02	NS
DRB1	25	11.6544	1	6.41E−04	*
DRB1	26	24.945	2	3.83E−06	*
DRB1	30	35.0811	5	1.45E−06	*
DRB1	31	15.869	2	3.58E−04	*
DRB1	32	1.3433	1	2.46E−01	NS
DRB1	33	15.2457	1	9.44E−05	*
DRB1	37	63.6089	4	5.05E−13	*
DRB1	38	1.5824	2	4.53E−01	NS
DRB1	40	0	1	1.00E+00	NS
DRB1	47	70.1772	1	< 2.22e−16	*
DRB1	57	18.4418	3	3.57E−04	*
DRB1	58	6.8992	1	8.62E−03	NS
DRB1	60	17.2657	2	1.78E−04	*
DRB1	67	30.5091	2	2.37E−07	*
DRB1	70	32.3764	2	9.32E−08	*
DRB1	71	121.9146	3	< 2.22e−16	*
DRB1	73	0	1	1.00E+00	NS
DRB1	74	25.6389	4	3.74E−05	*
DRB1	77	10.5184	1	1.18E−03	*
DRB1	78	11.3048	1	7.73E−04	*
DRB1	85	2.17	1	1.41E−01	NS
DRB1	86	58.2623	1	2.29E−14	*
HLA-B	80	14.6302	2	6.65E−04	*
HLA-C	73	20.4422	1	6.15E−06	*
HLA-C	77	2.1921	1	1.39E−01	NS
HLA-C	80	2.1921	1	1.39E−01	NS
HLA-C	90	14.7985	1	1.20E−04	*
HLA-C	73~90	20.7641	2	3.10E−05	*
HLA-C	77~80	2.3061	1	1.29E−01	NS
HLA-C	73~77~80~90	33.3303	5	3.24E−06	*

B. Association of DRB1 Exon-2 encoded Amino Acid Residues with Multiple Sclerosis
Locus	Position	Residue	Controls (N)	Cases (N)	OR	95% CI Lower	95% CI Upper	p-value	Significance 2
DRB1	11	L	108	57	0.5	0.35	0.71	5.41E−05	*
DRB1	11	S	339	315	0.92	0.75	1.12	0.39573	NS
DRB1	11	V	155	95	0.58	0.43	0.77	8.43E−05	*
DRB1	11	G	117	70	0.58	0.41	0.79	0.00048	*
DRB1	11	D	3	3	1.02	0.14	7.65	0.97874	NS
DRB1	11	P	116	280	3.23	2.51	4.15	< 2.22e−16	*
DRB1	13	F	119	67	0.54	0.39	0.75	0.0001	*
DRB1	13	S	296	289	1	0.81	1.23	0.97339	NS
DRB1	13	H	147	88	0.57	0.42	0.76	7.04E−05	*
DRB1	13	Y	117	70	0.58	0.41	0.79	0.00048	*
DRB1	13	G	43	26	0.61	0.35	1.02	0.04566	*
DRB1	13	R	116	280	3.23	2.51	4.15	< 2.22e−16	*
DRB1	14	E	721	750	1.74	1.26	2.41	0.00048	*
DRB1	14	K	117	70	0.58	0.41	0.79	0.00048	*
DRB1	25	R	721	750	1.74	1.26	2.41	0.00048	*
DRB1	25	Q	117	70	0.58	0.41	0.79	0.00048	*
DRB1	26	L	130	72	0.52	0.38	0.72	2.79E−05	*
DRB1	26	Y	83	125	1.64	1.21	2.23	0.001032	*
DRB1	26	F	625	623	1.08	0.86	1.36	0.5109	NS
DRB1	30	C	108	57	0.5	0.35	0.71	5.41E−05	*
DRB1	30	Y	588	675	1.98	1.56	2.52	6.39E−09	*
DRB1	30	L	117	70	0.58	0.41	0.79	0.00048	*
DRB1	30	G	3	3	1.02	0.14	7.65	0.97874	NS
DRB1	30	R	8	7	0.89	0.27	2.83	0.82809	NS
DRB1	30	H	14	8	0.58	0.21	1.49	0.21624	NS
DRB1	31	I	111	60	0.52	0.37	0.73	7.23E−05	*
DRB1	31	F	719	753	1.86	1.34	2.59	0.0001	*
DRB1	31	V	8	7	0.89	0.27	2.83	0.82809	NS
DRB1	33	N	691	732	1.77	1.32	2.38	7.04E−05	*
DRB1	33	H	147	88	0.57	0.42	0.76	7.04E−05	*
DRB1	37	S	224	337	1.91	1.55	2.37	6.34E−10	*
DRB1	37	N	167	201	1.3	1.03	1.66	0.024731	*
DRB1	37	Y	297	195	0.57	0.46	0.71	2.03E−07	*
DRB1	37	F	136	79	0.55	0.4	0.75	6.43E−05	*
DRB1	37	L	14	8	0.58	0.21	1.49	0.21624	NS
DRB1	47	Y	466	287	0.43	0.35	0.53	< 2.22e−16	*
DRB1	47	F	372	533	2.33	1.9	2.85	< 2.22e−16	*
DRB1	57	D	643	692	1.64	1.27	2.12	8.24E−05	*
DRB1	57	S	42	38	0.92	0.57	1.48	0.71967	NS
DRB1	57	V	134	81	0.58	0.42	0.78	0.000212	*
DRB1	57	A	19	9	0.48	0.19	1.12	0.06458	NS
DRB1	60	Y	685	729	1.79	1.34	2.39	3.88E−05	*
DRB1	60	S	134	82	0.58	0.43	0.79	0.000291	*
DRB1	60	H	19	9	0.48	0.19	1.12	0.06458	NS
DRB1	67	L	342	265	0.69	0.56	0.85	0.000331	*
DRB1	67	I	347	450	1.72	1.41	2.1	4.05E−08	*
DRB1	67	F	149	105	0.68	0.51	0.9	0.004919	*
DRB1	70	Q	404	509	1.76	1.44	2.15	1.4E−08	*
DRB1	70	D	404	292	0.59	0.49	0.73	2.02E−07	*
DRB1	70	R	30	19	0.64	0.34	1.18	0.12898	NS
DRB1	71	R	457	280	0.43	0.35	0.53	< 2.22e−16	*
DRB1	71	E	113	99	0.88	0.65	1.19	0.38958	NS
DRB1	71	K	174	180	1.07	0.84	1.37	0.55523	NS
DRB1	71	A	94	261	3.7	2.83	4.85	< 2.22e−16	*
DRB1	74	A	578	588	1.14	0.92	1.42	0.22315	NS
DRB1	74	R	80	122	1.66	1.21	2.27	0.000906	*
DRB1	74	E	33	22	0.67	0.37	1.2	0.15367	NS
DRB1	74	Q	117	70	0.58	0.41	0.79	0.00048	*
DRB1	74	L	30	18	0.6	0.31	1.13	0.092675	NS
DRB1	77	T	758	698	0.6	0.44	0.82	0.000906	*
DRB1	77	N	80	122	1.66	1.21	2.27	0.000906	*
DRB1	78	Y	718	747	1.71	1.24	2.36	0.000584	*
DRB1	78	V	120	73	0.58	0.42	0.8	0.000584	*
DRB1	86	G	483	318	0.47	0.38	0.57	1.56E−14	*
DRB1	86	V	355	502	2.15	1.76	2.63	1.56E−14	*

C. Association of HLA class I Amino Acids that Form KIR Ligand Epitopes with Multiple Sclerosis.
Locus	Position	Residue(s)	Controls (N)	Cases (N)	OR	95% CI Lower	95% CI Upper	p-value	Significance 3
HLA-B	80	N	520	574	1.43	1.16	1.76	6.38E−04	*
HLA-B	80	T	190	129	0.64	0.49	0.82	3.37E−04	*
HLA-B	80	I	128	117	0.92	0.7	1.22	5.64E−01	NS
HLA-C	73	T	361	264	0.63	0.51	0.77	4.83E−06	*
HLA-C	73	A	477	556	1.59	1.3	1.96	4.83E−06	*
HLA-C	90	A	416	329	0.68	0.56	0.83	9.77E−05	*
HLA-C	90	D	422	491	1.47	1.21	1.8	9.77E−05	*
HLA-C	73~90	A~A	55	65	1.22	0.83	1.81	2.90E−01	NS
HLA-C	73~90	A~D	422	492	1.47	1.2	1.79	1.01E−04	*
HLA-C	73~90	T~A	361	265	0.63	0.51	0.77	5.21E−06	*
HLA-C	73~77~80~90	A~N~K~A	6	16	2.75	1.02	8.63	2.84E−02	*
HLA-C	73~77~80~90	A~N~K~D	179	163	0.91	0.71	1.16	4.41E−01	NS
HLA-C	73~77~80~90	A~S~N~A	49	49	1.02	0.66	1.57	9.22E−01	NS
HLA-C	73~77~80~90	A~S~N~D	243	329	1.63	1.33	2.02	2.28E−06	*
HLA-C	73~77~80~90	T~N~K~A	146	115	0.77	0.59	1.01	5.48E−02	NS
HLA-C	73~77~80~90	T~S~N~A	215	150	0.65	0.51	0.82	2.69E−04	*

χ²_: Chi-squared value.

d.f.: Degrees of freedom.

OR: Odds Ratio.

¹After correcting for 28 comparisons, DRB1 significance was evaluated at the 1.79E−03 level. HLA-C significance was evaluated at the 7.14E−03 level (7 comparisons). Significant p-values are indicated with asterisks. NS: Not Significant.

²For each amino acid residue, the evaluation of significance was informed by the significance of heterogeneity for that position, as shown in Table 8A. Results are shown for positions that displayed significant heterogeneity.

³For each amino acid residue or combination of residues, the evaluation of significance was informed by the significance of heterogeneity for that position or positions, as shown in Table 8A. Results are shown for positions that displayed significant heterogeneity.